A tetrameric protein is a protein with a quaternary structure of four subunits. Homotetramers have four identical subunits, heterotetramers are complexes of different subunits. A tetramer can be assembled as dimer of dimers with two homodimer subunits, or two heterodimer subunits; the interactions between subunits forming a tetramer is determined by non covalent interaction. Hydrophobic effects, hydrogen bonds and electrostatic interactions are the primary sources for this binding process between subunits. For homotetrameric proteins such as Sorbitol dehydrogenase, the structure is believed to have evolved going from a monomeric to a dimeric and a tetrameric structure in evolution; the binding process in SDH and many other tetrameric enzymes can be described by the gain in free energy which can be determined from the rate of association and dissociation. The following image shows the assembly of the four subunits in SDH. Hydrogen bonding networks between subunits has been shown to be important for the stability of the tetrameric quaternary protein structure.
For example, a study of SDH which used diverse methods such as protein sequence alignments, structural comparisons, energy calculations, gel filtration experiments and enzyme kinetics experiments, could reveal an important hydrogen bonding network which stabilizes the tetrameric quaternary structure in mammalian SDH. In immunology, MHC tetramers can be used in tetramer assays, to quantify numbers of antigen-specific T cells. MHC tetramers are based on recombinant class I molecules that, through the action of bacterial BirA, have been biotinylated; these molecules are folded with the peptide of interest and β2M and tetramerized by a fluorescently labeled streptavidin. This tetramer reagent will label T cells that express T cell receptors that are specific for a given peptide-MHC complex. For example, a Kb/FAPGNYPAL tetramer will bind to Sendai virus specific cytotoxic T cell in a C57BL/6 mouse. Antigen specific responses can be measured as CD8+, tetramer+ T cells as a fraction of all CD8+ lymphocytes.
The reason for using a tetramer, as opposed to a single labeled MHC class I molecule is that the tetrahedral tetramers can bind to three TCRs at once, allowing specific binding in spite of the low affinity of the typical class I-peptide-TCR interaction. MHC class II tetramers can be made although these are more difficult to work with practically. T-cell Group - Cardiff University
The Mediterranean Sea is a sea connected to the Atlantic Ocean, surrounded by the Mediterranean Basin and completely enclosed by land: on the north by Southern Europe and Anatolia, on the south by North Africa and on the east by the Levant. Although the sea is sometimes considered a part of the Atlantic Ocean, it is identified as a separate body of water. Geological evidence indicates that around 5.9 million years ago, the Mediterranean was cut off from the Atlantic and was or desiccated over a period of some 600,000 years, the Messinian salinity crisis, before being refilled by the Zanclean flood about 5.3 million years ago. It covers an approximate area of 2.5 million km2, representing 0.7 % of the global ocean surface, but its connection to the Atlantic via the Strait of Gibraltar-the narrow strait that connects the Atlantic Ocean to the Mediterranean Sea and separates Spain in Europe from Morocco in Africa- is only 14 km wide. In oceanography, it is sometimes called the Eurafrican Mediterranean Sea or the European Mediterranean Sea to distinguish it from mediterranean seas elsewhere.
The Mediterranean Sea has an average depth of 1,500 m and the deepest recorded point is 5,267 m in the Calypso Deep in the Ionian Sea. The sea is bordered on the north by Europe, the east by Asia, in the south by Africa, it is located between latitudes 30° and 46° N and longitudes 6° W and 36° E. Its west-east length, from the Strait of Gibraltar to the Gulf of Iskenderun, on the southwestern coast of Turkey, is 4,000 km; the sea's average north-south length, from Croatia's southern shore to Libya, is 800 km. The sea was an important route for merchants and travellers of ancient times that allowed for trade and cultural exchange between emergent peoples of the region; the history of the Mediterranean region is crucial to understanding the origins and development of many modern societies. The countries surrounding the Mediterranean in clockwise order are Spain, Monaco, Slovenia, Croatia and Herzegovina, Albania, Turkey, Lebanon, Egypt, Tunisia and Morocco. In addition, the Gaza Strip and the British Overseas Territories of Gibraltar and Akrotiri and Dhekelia have coastlines on the sea.
The Ancient Greeks called the Mediterranean ἡ θάλασσα or sometimes ἡ μεγάλη θάλασσα, ἡ ἡμέτερα θάλασσα, or ἡ θάλασσα ἡ καθ'ἡμᾶς. The Romans called it Mare Mare Internum and, starting with the Roman Empire, Mare Nostrum; the term Mare Mediterrāneum appears later: Solinus used it in the 3rd century, but the earliest extant witness to it is in the 6th century, in Isidore of Seville. It means'in the middle of land, inland' in Latin, a compound of medius, -āneus; the Latin word is a calque of Greek μεσόγειος, from μέσος and γήινος, from γῆ. The original meaning may have been'the sea in the middle of the earth', rather than'the sea enclosed by land'; the Carthaginians called it the "Syrian Sea". In ancient Syrian texts, Phoenician epics and in the Hebrew Bible, it was known as the "Great Sea" or as "The Sea". Another name was the "Sea of the Philistines", from the people inhabiting a large portion of its shores near the Israelites. In Modern Hebrew, it is called HaYam HaTikhon'the Middle Sea'. In Modern Arabic, it is known as al-Baḥr al-Mutawassiṭ'the Middle Sea'.
In Islamic and older Arabic literature, it was Baḥr al-Rūm'the Sea of the Romans' or'the Roman Sea'. At first, that name referred to only the Eastern Mediterranean, but it was extended to the whole Mediterranean. Other Arabic names were Baḥr al-šām'the Sea of Syria' and Baḥr al-Maghrib'the Sea of the West'. In Turkish, it is the Akdeniz'the White Sea'; the origin of the name is not clear, as it is not known in earlier Greek, Byzantine or Islamic sources. It may be to contrast with the Black Sea. In Persian, the name was translated as Baḥr-i Safīd, used in Ottoman Turkish, it is the origin of the colloquial Greek phrase Άσπρη Θάλασσα. Johann Knobloch claims that in Classical Antiquity, cultures in the Levant used colours to refer to the cardinal points: black referred to the north, yellow or blue to east, red to south, white to west; this would explain both the Turkish Akdeniz and the Arab nomenclature described above. Several ancient civilizations were located around the Mediterranean shores and were influenced by their proximity to the sea.
It provided routes for trade and war, as well as food for numerous communities throughout the ages. Due to the shared climate and access to the sea, c
Actin is a family of globular multi-functional proteins that form microfilaments. It is found in all eukaryotic cells, where it may be present at a concentration of over 100 μM. An actin protein is the monomeric subunit of two types of filaments in cells: microfilaments, one of the three major components of the cytoskeleton, thin filaments, part of the contractile apparatus in muscle cells, it can be present as either a free monomer called G-actin or as part of a linear polymer microfilament called F-actin, both of which are essential for such important cellular functions as the mobility and contraction of cells during cell division. Actin participates in many important cellular processes, including muscle contraction, cell motility, cell division and cytokinesis and organelle movement, cell signaling, the establishment and maintenance of cell junctions and cell shape. Many of these processes are mediated by extensive and intimate interactions of actin with cellular membranes. In vertebrates, three main groups of actin isoforms, alpha and gamma have been identified.
The alpha actins, found in muscle tissues, are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton, as mediators of internal cell motility, it is believed that the diverse range of structures formed by actin enabling it to fulfill such a large range of functions is regulated through the binding of tropomyosin along the filaments. A cell's ability to dynamically form microfilaments provides the scaffolding that allows it to remodel itself in response to its environment or to the organism's internal signals, for example, to increase cell membrane absorption or increase cell adhesion in order to form cell tissue. Other enzymes or organelles such as cilia can be anchored to this scaffolding in order to control the deformation of the external cell membrane, which allows endocytosis and cytokinesis, it can produce movement either by itself or with the help of molecular motors. Actin therefore contributes to processes such as the intracellular transport of vesicles and organelles as well as muscular contraction and cellular migration.
It therefore plays an important role in embryogenesis, the healing of wounds and the invasivity of cancer cells. The evolutionary origin of actin can be traced to prokaryotic cells. Actin homologs from prokaryotes and archaea polymerize into different helical or linear filaments consisting of one or multiple strands; however the in-strand contacts and nucleotide binding sites are preserved in prokaryotes and in archaea. Lastly, actin plays an important role in the control of gene expression. A large number of illnesses and diseases are caused by mutations in alleles of the genes that regulate the production of actin or of its associated proteins; the production of actin is key to the process of infection by some pathogenic microorganisms. Mutations in the different genes that regulate actin production in humans can cause muscular diseases, variations in the size and function of the heart as well as deafness; the make-up of the cytoskeleton is related to the pathogenicity of intracellular bacteria and viruses in the processes related to evading the actions of the immune system.
Actin was first observed experimentally in 1887 by W. D. Halliburton, who extracted a protein from muscle that'coagulated' preparations of myosin that he called "myosin-ferment". However, Halliburton was unable to further refine his findings, the discovery of actin is credited instead to Brunó Ferenc Straub, a young biochemist working in Albert Szent-Györgyi's laboratory at the Institute of Medical Chemistry at the University of Szeged, Hungary. In 1942, Straub developed a novel technique for extracting muscle protein that allowed him to isolate substantial amounts of pure actin. Straub's method is the same as that used in laboratories today. Szent-Gyorgyi had described the more viscous form of myosin produced by slow muscle extractions as'activated' myosin, since Straub's protein produced the activating effect, it was dubbed actin. Adding ATP to a mixture of both proteins causes a decrease in viscosity; the hostilities of World War II meant Szent-Gyorgyi and Straub were unable to publish the work in Western scientific journals.
Actin therefore only became well known in the West in 1945, when their paper was published as a supplement to the Acta Physiologica Scandinavica. Straub continued to work on actin, in 1950 reported that actin contains bound ATP and that, during polymerization of the protein into microfilaments, the nucleotide is hydrolyzed to ADP and inorganic phosphate. Straub suggested that the transformation of ATP-bound actin to ADP-bound actin played a role in muscular contraction. In fact, this is true only in smooth muscle, was not supported through experimentation until 2001; the amino acid sequencing of actin was completed by M. Elzinga and co-workers in 1973; the crystal structure of G-actin was solved in 1990 by colleagues. In the same year, a model for F-actin was proposed by Holmes and colleagues following experiments using co-crystallization with different proteins; the procedure of co-crystallization with different proteins was used during the following years, until in 2001 the isolated protein was crystallized along with ADP.
However, there is still no high-resolution X-ray structure of F-actin. The crystallization of F-actin was possible due to the use of a rhodamine conjugate that impedes polymerization by blocking the amino acid cys-374. Christine
Malaysia is a country in Southeast Asia. The federal constitutional monarchy consists of 13 states and three federal territories, separated by the South China Sea into two sized regions, Peninsular Malaysia and East Malaysia. Peninsular Malaysia shares a land and maritime border with Thailand and maritime borders with Singapore and Indonesia. East Malaysia shares land and maritime borders with Brunei and Indonesia and a maritime border with the Philippines and Vietnam. Kuala Lumpur is the national capital and largest city while Putrajaya is the seat of federal government. With a population of over 30 million, Malaysia is the world's 44th most populous country; the southernmost point of continental Eurasia, Tanjung Piai, is in Malaysia. In the tropics, Malaysia is one of 17 megadiverse countries, with large numbers of endemic species. Malaysia has its origins in the Malay kingdoms which, from the 18th century, became subject to the British Empire, along with the British Straits Settlements protectorate.
Peninsular Malaysia was unified as the Malayan Union in 1946. Malaya was restructured as the Federation of Malaya in 1948, achieved independence on 31 August 1957. Malaya united with North Borneo and Singapore on 16 September 1963 to become Malaysia. In 1965, Singapore was expelled from the federation; the country is multi-cultural, which plays a large role in its politics. About half the population is ethnically Malay, with large minorities of Malaysian Chinese, Malaysian Indians, indigenous peoples. While recognising Islam as the country's established religion, the constitution grants freedom of religion to non-Muslims; the government system is modelled on the Westminster parliamentary system and the legal system is based on common law. The head of state is the king, known as the Yang di-Pertuan Agong, he is an elected monarch chosen from the hereditary rulers of the nine Malay states every five years. The head of government is the Prime Minister; the country's official language is a standard form of the Malay language.
English remains an active second language. Since independence, Malaysian GDP has grown at an average of 6.5% per annum for 50 years. The economy has traditionally been fuelled by its natural resources, but is expanding in the sectors of science, tourism and medical tourism. Today, Malaysia has a newly industrialised market economy, ranked fourth largest in Southeast Asia and 38th largest in the world, it is a founding member of the Association of Southeast Asian Nations, the East Asia Summit and the Organisation of Islamic Cooperation, a member of Asia-Pacific Economic Cooperation, the Commonwealth of Nations, the Non-Aligned Movement. The name "Malaysia" is a combination of the word "Malay" and the Latin-Greek suffix "-sia"/-σία; the word "melayu" in Malay may derive from the Tamil words "malai" and "ur" meaning "mountain" and "city, land", respectively. "Malayadvipa" was the word used by ancient Indian traders. Whether or not it originated from these roots, the word "melayu" or "mlayu" may have been used in early Malay/Javanese to mean to accelerate or run.
This term was applied to describe the strong current of the river Melayu in Sumatra. The name was adopted by the Melayu Kingdom that existed in the seventh century on Sumatra. Before the onset of European colonisation, the Malay Peninsula was known natively as "Tanah Melayu". Under a racial classification created by a German scholar Johann Friedrich Blumenbach, the natives of maritime Southeast Asia were grouped into a single category, the Malay race. Following the expedition of French navigator Jules Dumont d'Urville to Oceania in 1826, he proposed the terms of "Malaysia", "Micronesia" and "Melanesia" to the Société de Géographie in 1831, distinguishing these Pacific cultures and island groups from the existing term "Polynesia". Dumont d'Urville described Malaysia as "an area known as the East Indies". In 1850, the English ethnologist George Samuel Windsor Earl, writing in the Journal of the Indian Archipelago and Eastern Asia, proposed naming the islands of Southeast Asia as "Melayunesia" or "Indunesia", favouring the former.
In modern terminology, "Malay" remains the name of an ethnoreligious group of Austronesian people predominantly inhabiting the Malay Peninsula and portions of the adjacent islands of Southeast Asia, including the east coast of Sumatra, the coast of Borneo, smaller islands that lie between these areas. The state that gained independence from the United Kingdom in 1957 took the name the "Federation of Malaya", chosen in preference to other potential names such as "Langkasuka", after the historic kingdom located at the upper section of the Malay Peninsula in the first millennium CE; the name "Malaysia" was adopted in 1963 when the existing states of the Federation of Malaya, plus Singapore, North Borneo and Sarawak formed a new federation. One theory posits the name was chosen so that "si" represented the inclusion of Singapore, North Borneo, Sarawak to Malaya in 1963. Politicians in the Philippines contemplated renaming their state "Malaysia" before the modern country took the name. Evidence of modern human habitation in Malaysia dates back 40,000 years.
In the Malay Peninsula, the first inhabitants are thought to be Negritos. Traders and settlers from India and China arrived as early as the first century AD, establishing trading ports and coastal towns in the second and third centuries, their presence resulted in strong Indian and Chinese influences on the local cultures, the people of the Malay Peninsula adopted the religions of Hinduism and Buddhism. Sanskrit inscriptions appear as early as the fifth century; the Kingdom of
Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane in eukaryotic cells. Spectrin forms pentagonal or hexagonal arrangements, forming a scaffold and playing an important role in maintenance of plasma membrane integrity and cytoskeletal structure; the hexagonal arrangements are formed by tetramers of spectrin subunits associating with short actin filaments at either end of the tetramer. These short actin filaments act as junctional complexes allowing the formation of the hexagonal mesh; the protein is named spectrin since it was first isolated as a major protein component of human red blood cells, treated with mild detergents. In the light microscope the basic shape of the red blood cell could still be seen as the spectrin-containing submembranous cytoskeleton preserved the shape of the cell in outline; this became known as a red blood cell "ghost", so the major protein of the ghost was named spectrin. In certain types of brain injury such as diffuse axonal injury, spectrin is irreversibly cleaved by the proteolytic enzyme calpain, destroying the cytoskeleton.
Spectrin cleavage causes the membrane to form blebs and to be degraded leading to the death of the cell. Spectrin subunits may be cleaved by caspase family enzymes, calpain and caspase produce different spectrin breakdown products which can be detected by western blotting with appropriate antibodies. Calpain cleavage may indicate activation of necrosis; the convenience of using erythrocytes compared to other cell types means they have become the standard model for the investigation of the spectrin cytoskeleton. Dimeric spectrin is formed by the lateral association of βI monomers to form a dimer. Dimers associate in a head-to-head formation to produce the tetramer. End-to-end association of these tetramers with short actin filaments produces the hexagonal complexes observed. In humans, association with the intracellular face of the plasma membrane is by indirect interaction, through direct interactions with protein 4.1 and ankyrin, with the transmembrane ion transporter band 3 Protein 4.2 binds the spectrin tail region to the transmembrane protein glycophorin A.
In animals, spectrin forms the meshwork. The erythrocyte model demonstrates the importance of the spectrin cytoskeleton in that mutations in spectrin cause hereditary defects of the erythrocyte, including hereditary elliptocytosis and hereditary spherocytosis. There are three spectrins in invertebrates, α,β and βH. Mutations in βH spectrin in C. elegans cause defects in morphogenesis resulting in a shorter, but otherwise normal, animal that moves and reproduces. These animals are called "sma" for their small phenotype and carry mutations in the C. elegans sma-1 gene. A mutation in β spectrin in C. elegans results in an uncoordinated phenotype in which the worms are paralysed and much shorter than wild-type. In addition to the morphological effects, the Unc-70 mutation produce defective neurons. Neuron numbers are normal but neuronal outgrowth was defective. Spectrin plays a role in Drosophila neurons. Knock-out of α or β spectrin in D. melanogaster results in neurons that are morphologically normal but have reduced neurotransmission at the neuromuscular junction.
In animals, spectrin forms the meshwork. The spectrin gene family has undergone expansion during evolution. Rather than the one α and two β genes in invertebrates, there are two α spectrins and five β spectrins, named in the order of discovery. In humans, the genes are: Alpha: SPTA1, SPTAN1 Beta: SPTB, SPTBN1, SPTBN2, SPTBN4, SPTBN5The production of spectrin is promoted by the transcription factor GATA1; some evidence for the role of spectrins in muscle tissues exist. In myocardial cells, aII spectrin distribution is coincident with Z-discs and the plasma membrane of myofibrils. Additionally, mice with an ankyrin knock-out have disrupted calcium homeostasis in the myocardia. Affected mice have disrupted sarcomere morphology. In this experimental model ryanodine and IP3 receptors have abnormal distribution in cultured myocytes; the calcium signaling of the cultured cells is disrupted. In humans, a mutation within the AnkB gene results in the long QT syndrome and sudden death, strengthening the evidence for a role for the spectrin cytoskeleton in excitable tissue.
Proteopedia 2fot the complex between calmodulin and alpha11spectrin Spectrin repeat Glycophorin C, helps anchor spectrin-actin cytoskeleton to cell membrane in erythrocytes
In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers; the word dimer has roots meaning "two parts", di- + -mer. A protein dimer is a type of protein quaternary structure. A protein homodimer is formed by two identical proteins. A protein heterodimer is formed by two different proteins. Most protein dimers in biochemistry are not connected by covalent bonds. An example of a non-covalent heterodimer is the enzyme reverse transcriptase, composed of two different amino acid chains. An exception is dimers that are linked by disulfide bridges such as the homodimeric protein NEMO; some proteins contain specialized domains to ensure specificity. Antibodies Receptor tyrosine kinases Transcription factors Leucine zipper motif proteins Nuclear receptors 14-3-3 proteins G protein-coupled receptors G protein βγ-subunit dimer Kinesin Triosephosphateisomerase Alcohol dehydrogenase Factor XI Factor XIII Toll-like receptor Fibrinogen Variable surface glycoproteins of the Trypanosoma parasite Tubulin Type II restriction enzymes Dimer Protein trimer Oligomer ProtCID
Africa is the world's second largest and second most-populous continent, being behind Asia in both categories. At about 30.3 million km2 including adjacent islands, it covers 6% of Earth's total surface area and 20% of its land area. With 1.2 billion people as of 2016, it accounts for about 16% of the world's human population. The continent is surrounded by the Mediterranean Sea to the north, the Isthmus of Suez and the Red Sea to the northeast, the Indian Ocean to the southeast and the Atlantic Ocean to the west; the continent includes various archipelagos. It contains 54 recognised sovereign states, nine territories and two de facto independent states with limited or no recognition; the majority of the continent and its countries are in the Northern Hemisphere, with a substantial portion and number of countries in the Southern Hemisphere. Africa's average population is the youngest amongst all the continents. Algeria is Africa's largest country by area, Nigeria is its largest by population. Africa central Eastern Africa, is accepted as the place of origin of humans and the Hominidae clade, as evidenced by the discovery of the earliest hominids and their ancestors as well as ones that have been dated to around 7 million years ago, including Sahelanthropus tchadensis, Australopithecus africanus, A. afarensis, Homo erectus, H. habilis and H. ergaster—the earliest Homo sapiens, found in Ethiopia, date to circa 200,000 years ago.
Africa encompasses numerous climate areas. Africa hosts a large diversity of ethnicities and languages. In the late 19th century, European countries colonised all of Africa. African nations cooperate through the establishment of the African Union, headquartered in Addis Ababa. Afri was a Latin name used to refer to the inhabitants of then-known northern Africa to the west of the Nile river, in its widest sense referred to all lands south of the Mediterranean; this name seems to have referred to a native Libyan tribe, an ancestor of modern Berbers. The name had been connected with the Phoenician word ʿafar meaning "dust", but a 1981 hypothesis has asserted that it stems from the Berber word ifri meaning "cave", in reference to cave dwellers; the same word may be found in the name of the Banu Ifran from Algeria and Tripolitania, a Berber tribe from Yafran in northwestern Libya. Under Roman rule, Carthage became the capital of the province it named Africa Proconsularis, following its defeat of the Carthaginians in the Third Punic War in 146 BC, which included the coastal part of modern Libya.
The Latin suffix -ica can sometimes be used to denote a land. The Muslim region of Ifriqiya, following its conquest of the Byzantine Empire's Exarchatus Africae preserved a form of the name. According to the Romans, Africa lay to the west of Egypt, while "Asia" was used to refer to Anatolia and lands to the east. A definite line was drawn between the two continents by the geographer Ptolemy, indicating Alexandria along the Prime Meridian and making the isthmus of Suez and the Red Sea the boundary between Asia and Africa; as Europeans came to understand the real extent of the continent, the idea of "Africa" expanded with their knowledge. Other etymological hypotheses have been postulated for the ancient name "Africa": The 1st-century Jewish historian Flavius Josephus asserted that it was named for Epher, grandson of Abraham according to Gen. 25:4, whose descendants, he claimed, had invaded Libya. Isidore of Seville in his 7th-century Etymologiae XIV.5.2. Suggests "Africa comes from the Latin aprica, meaning "sunny".
Massey, in 1881, stated that Africa is derived from the Egyptian af-rui-ka, meaning "to turn toward the opening of the Ka." The Ka is the energetic double of every person and the "opening of the Ka" refers to a womb or birthplace. Africa would be, for the Egyptians, "the birthplace." Michèle Fruyt in 1976 proposed linking the Latin word with africus "south wind", which would be of Umbrian origin and mean "rainy wind". Robert R. Stieglitz of Rutgers University in 1984 proposed: "The name Africa, derived from the Latin *Aphir-ic-a, is cognate to Hebrew Ophir." Ibn Khallikan and some other historians claim that the name of Africa came from a Himyarite king called Afrikin ibn Kais ibn Saifi called "Afrikus son of Abrahah" who subdued Ifriqiya. Africa is considered by most paleoanthropologists to be the oldest inhabited territory on Earth, with the human species originating from the continent. During the mid-20th century, anthropologists discovered many fossils and evidence of human occupation as early as 7 million years ago.
Fossil remains of several species of early apelike humans thought to have evolved into modern man, such as Australopithecus afarensis (radiometrically dated to 3.9–3.0 million years BP, Paranthropus boisei and Homo ergaster have been discovered. After the evolution of Homo sapiens sapiens 150,000 to 100,000 years BP in Africa, the continent was populated by groups of hunter-gatherers; these first modern humans left Africa and populated the rest of the globe during the Out of Africa II migration dated to 50,000 years BP, exiting the continent eith