A basic helix-loop-helix is a protein structural motif that characterizes a family of transcription factors. It should not be confused with the helix-turn-helix domain, the motif is characterized by two α-helices connected by a loop. In general, transcription factors including this domain are dimeric, each with one helix containing basic amino acid residues that facilitate DNA binding. In general, one helix is smaller, due to the flexibility of the loop, the larger helix typically contains the DNA-binding regions. BHLH proteins typically bind to a sequence called an E-box. The canonical E-box is CACGTG, however some bHLH transcription factors, notably those of the family, bind to related non-palindromic sequences. Scleraxis Neurogenins MAX OLIG1, OLIG2 TCF4 bHLH transcription factors are important in development or cell activity. BMAL1-Clock is a transcription complex in the molecular circadian clock. Other genes, like c-Myc and HIF-1, have linked to cancer due to their effects on cell growth.
Since many bHLH transcription factors are heterodimeric, their activity is highly regulated by the dimerization of the subunits. One subunits expression or availability is controlled, whereas the other subunit is constitutively expressed. Many of the regulatory proteins, such as the Drosophila extramacrochaetae protein, have the helix-loop-helix structure but lack the basic region. They are, able to form heterodimers with proteins that have the bHLH structure,1989, Murre et al. showed that dimers of various bHLH proteins bind to a short DNA motif. This E-box consists of the DNA sequence CANNTG, where N can be any nucleotide,1994, Wharton et al. identified asymmetric E-boxes bound by a subset of bHLH proteins with PAS domains, including Single-minded and the aromatic hydrocarbon receptor. 1995, Semenzas group identifies hypoxia-inducible factor as a heterodimer that binds a related asymmetric E-box. 2009, Grove, De Masi et al. identified novel short DNA motifs, bound by a subset of bHLH proteins, which they defined as E-box-like sequences.
These are in the form of CAYRMK, where Y stands for C or T, R is A or G, M is A or C and K is G or T
The Basic Leucine Zipper Domain is found in many DNA binding eukaryotic proteins. One part of the domain contains a region that mediates sequence specific DNA binding properties, the DNA binding region comprises a number of basic amino acids such as arginine and lysine. Proteins containing this domain are transcription factors, BZIP transcription factors are found in all organisms. An evolutionary study from 2008 revealed that 4 bZIP genes were encoded by the genome of the most recent common ancestor of all plants
A chromosome is a DNA molecule with part or all of the genetic material of an organism. Prokaryotes usually have one single circular chromosome, whereas most eukaryotes are diploid, chromosomes in eukaryotes are composed of chromatin fiber. Chromatin fiber is made of nucleosomes, a nucleosome is a histone octamer with part of a longer DNA strand attached to and wrapped around it. Chromatin fiber, together with associated proteins is known as chromatin, chromatin is present in most cells, with a few exceptions, for example, red blood cells. Occurring only in the nucleus of cells, chromatin contains the vast majority of DNA, except for a small amount inherited maternally. Chromosomes are normally visible under a microscope only when the cell is undergoing the metaphase of cell division. Before this happens every chromosome is copied once, and the copy is joined to the original by a centromere resulting in an X-shaped structure, the original chromosome and the copy are now called sister chromatids.
During metaphase, when a chromosome is in its most condensed state, in this highly condensed form chromosomes are easiest to distinguish and study. In prokaryotic cells, chromatin occurs free-floating in cytoplasm, as these cells lack organelles, the main information-carrying macromolecule is a single piece of coiled double-helix DNA, containing many genes, regulatory elements and other noncoding DNA. The DNA-bound macromolecules are proteins that serve to package the DNA, chromosomes vary widely between different organisms. Some species such as certain bacteria contain plasmids or other extrachromosomal DNA and these are circular structures in the cytoplasm that contain cellular DNA and play a role in horizontal gene transfer. Chromosomal recombination during meiosis and subsequent sexual reproduction plays a significant role in genetic diversity. In prokaryotes and viruses, the DNA is often densely packed and organized, in the case of archaea, by homologs to eukaryotic histones, small circular genomes called plasmids are often found in bacteria and in mitochondria and chloroplasts, reflecting their bacterial origins.
Some use the term chromosome in a sense, to refer to the individualized portions of chromatin in cells. However, others use the concept in a sense, to refer to the individualized portions of chromatin during cell division. The word chromosome comes from the Greek χρῶμα and σῶμα, describing their strong staining by particular dyes, Virchow and Bütschli were among the first scientists who recognized the structures now so familiar to everyone as chromosomes. The term was coined by von Waldeyer-Hartz, referring to the term chromatin, in a series of experiments beginning in the mid-1880s, Theodor Boveri gave the definitive demonstration that chromosomes are the vectors of heredity. His two principles were the continuity of chromosomes and the individuality of chromosomes and it is the second of these principles that was so original
A gene is a locus of DNA which is made up of nucleotides and is the molecular unit of heredity. The transmission of genes to an offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes, genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes as well as gene–environment interactions, genes can acquire mutations in their sequence, leading to different variants, known as alleles, in the population. These alleles encode slightly different versions of a protein, which cause different phenotypical traits, usage of the term having a gene typically refers to containing a different allele of the same, shared gene. Genes evolve due to natural selection or survival of the fittest of the alleles, the concept of a gene continues to be refined as new phenomena are discovered. For example, regulatory regions of a gene can be far removed from its coding regions, some viruses store their genome in RNA instead of DNA and some gene products are functional non-coding RNAs.
The existence of discrete inheritable units was first suggested by Gregor Mendel, from 1857 to 1864, in Brno, he studied inheritance patterns in 8000 common edible pea plants, tracking distinct traits from parent to offspring. He described these mathematically as 2n combinations where n is the number of differing characteristics in the original peas, although he did not use the term gene, he explained his results in terms of discrete inherited units that give rise to observable physical characteristics. This description prefigured the distinction between genotype and phenotype, charles Darwin developed a theory of inheritance he termed pangenesis, from Greek pan and genesis / genos. Darwin used the term gemmule to describe hypothetical particles that would mix during reproduction, de Vries called these units pangenes, after Darwins 1868 pangenesis theory. In 1909 the Danish botanist Wilhelm Johannsen shortened the name to gene, advances in understanding genes and inheritance continued throughout the 20th century.
Deoxyribonucleic acid was shown to be the repository of genetic information by experiments in the 1940s to 1950s. In the early 1950s the prevailing view was that the genes in a chromosome acted like discrete entities, indivisible by recombination, this body of research established the central dogma of molecular biology, which states that proteins are translated from RNA, which is transcribed from DNA. This dogma has since shown to have exceptions, such as reverse transcription in retroviruses. The modern study of genetics at the level of DNA is known as molecular genetics, in 1972, Walter Fiers and his team at the University of Ghent were the first to determine the sequence of a gene, the gene for Bacteriophage MS2 coat protein. The subsequent development of chain-termination DNA sequencing in 1977 by Frederick Sanger improved the efficiency of sequencing, an automated version of the Sanger method was used in early phases of the Human Genome Project. The theories developed in the 1930s and 1940s to integrate molecular genetics with Darwinian evolution are called the evolutionary synthesis
Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, a linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide, short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides, or sometimes oligopeptides. The individual amino acid residues are bonded together by peptide bonds, the sequence of amino acid residues in a protein is defined by the sequence of a gene, which is encoded in the genetic code. In general, the code specifies 20 standard amino acids, however. Sometimes proteins have non-peptide groups attached, which can be called prosthetic groups or cofactors, proteins can work together to achieve a particular function, and they often associate to form stable protein complexes.
Once formed, proteins only exist for a period of time and are degraded and recycled by the cells machinery through the process of protein turnover. A proteins lifespan is measured in terms of its half-life and covers a wide range and they can exist for minutes or years with an average lifespan of 1–2 days in mammalian cells. Abnormal and or misfolded proteins are degraded more rapidly due to being targeted for destruction or due to being unstable. Like other biological macromolecules such as polysaccharides and nucleic acids, proteins are essential parts of organisms, many proteins are enzymes that catalyse biochemical reactions and are vital to metabolism. Proteins have structural or mechanical functions, such as actin and myosin in muscle and the proteins in the cytoskeleton, other proteins are important in cell signaling, immune responses, cell adhesion, and the cell cycle. In animals, proteins are needed in the diet to provide the essential amino acids that cannot be synthesized, digestion breaks the proteins down for use in the metabolism.
Methods commonly used to study structure and function include immunohistochemistry, site-directed mutagenesis, X-ray crystallography, nuclear magnetic resonance. Most proteins consist of linear polymers built from series of up to 20 different L-α-amino acids, all proteinogenic amino acids possess common structural features, including an α-carbon to which an amino group, a carboxyl group, and a variable side chain are bonded. Only proline differs from this structure as it contains an unusual ring to the N-end amine group. The amino acids in a chain are linked by peptide bonds. Once linked in the chain, an individual amino acid is called a residue, and the linked series of carbon, nitrogen. The peptide bond has two forms that contribute some double-bond character and inhibit rotation around its axis, so that the alpha carbons are roughly coplanar
A base pair is a unit consisting of two nucleobases bound to each other by hydrogen bonds. They form the blocks of the DNA double helix. Dictated by specific hydrogen bonding patterns, Watson-Crick base pairs allow the DNA helix to maintain a regular helical structure that is dependent on its nucleotide sequence. The complementary nature of this structure provides a backup copy of all genetic information encoded within double-stranded DNA. Many DNA-binding proteins can recognize specific base pairing patterns that identify particular regulatory regions of genes, intramolecular base pairs can occur within single-stranded nucleic acids. The size of a gene or an organisms entire genome is often measured in base pairs because DNA is usually double-stranded. Hence, the number of base pairs is equal to the number of nucleotides in one of the strands. The haploid human genome is estimated to be about 3.2 billion bases long and to contain 20, a kilobase is a unit of measurement in molecular biology equal to 1000 base pairs of DNA or RNA.
The total amount of related DNA base pairs on Earth is estimated at 5.0 x 1037, in comparison, the total mass of the biosphere has been estimated to be as much as 4 TtC. Hydrogen bonding is the interaction that underlies the base-pairing rules described above. Appropriate geometrical correspondence of hydrogen donors and acceptors allows only the right pairs to form stably. Purine-pyrimidine base pairing of AT or GC or UA results in proper duplex structure, the only other purine-pyrimidine pairings would be AC and GT and UG, these pairings are mismatches because the patterns of hydrogen donors and acceptors do not correspond. The GU pairing, with two bonds, does occur fairly often in RNA. Higher GC content results in higher melting temperatures, it is, therefore, on the converse, regions of a genome that need to separate frequently — for example, the promoter regions for often-transcribed genes — are comparatively GC-poor. GC content and melting temperature must be taken into account when designing primers for PCR reactions, the following DNA sequences illustrate pair double-stranded patterns.
By convention, the top strand is written from the 5 end to the 3 end and this is due to their isosteric chemistry. One common mutagenic base analog is 5-bromouracil, which resembles thymine, most intercalators are large polyaromatic compounds and are known or suspected carcinogens. Examples include ethidium bromide and acridine, an unnatural base pair is a designed subunit of DNA which is created in a laboratory and does not occur in nature
A leucine zipper, a. k. a. leucine scissors, is a common three-dimensional structural motif in proteins. Leucine zippers are a domain of the bZIP class of eukaryotic transcription factors. The bZIP domain is 60 to 80 amino acids in length with a highly conserved DNA binding basic region, the leucine zipper is a common three-dimensional structural motif in proteins and it has that name because leucines occur every seven amino acids in the dimerization domain. The localization of the leucines are critical for the DNA binding to the proteins, leucine zippers are present in both eukaryotic and prokaryotic regulatory proteins, but are mainly a feature of eukaryotes. The mechanism of regulation by bZIP proteins has been studied in detail. Most bZIP proteins show high binding affinity for the ACGT motifs, which include CACGTG, GACGTC, TACGTA, AACGTT, a small number of bZIP factors such as OsOBF1 can recognize palindromic sequences. However, the others, including LIP19, OsZIP-2a, and OsZIP-2b, these bZIP proteins form heterodimers with other bZIPs to regulate transcriptional activities.
Leucine zipper is created by the dimerization of two specific alpha helix monomers bound to DNA, the bZIP interacts with the DNA via its N-terminal, where the lysines and arginines are located, these basic residues interact in the major groove of the DNA, forming sequence-specific interactions. The leucine zipper is located in the C-terminal region of the bZIP, when that alpha helix dimerizes, the zipper is formed. The hydrophobic side of the forms a dimer with itself or another similar helix. The hydrophilic side of the helix interacts with the water in the solvent, leucine zipper domains are considered a subtype of coiled coils, which are built by two or more alpha helices that are wound around each other to form a supercoil. Coiled coils contain 3- and 4-residue repeats whose hydrophobicity pattern and residue composition is compatible with the structure of amphipathic alpha-helices, in the case of leucine zippers, leucines are predominant at the d position of the heptad repeat. They are referred to as coiled coils unless they are proven to be important for protein function, if that is the case, they are annotated in the “domain” subsection, which would be the bZIP domain.
Leucine zipper regulatory proteins include c-fos and c-jun, important regulators of normal development, as well as myc family members including myc, max, if they are overproduced or mutated in a vital area, they may generate cancer. Leucine zippers at the US National Library of Medicine Medical Subject Headings