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Rubicon Homology Domain
The Rubicon homology domain (also known as RH domain) is an evolutionarily conserved protein domain of approximately 250 amino acids that mediates protein–protein interaction. RH domains are present in several human proteins involved in regulation of autophagy and endosomal trafficking. While not all RH domains have been characterized, those of human Rubicon and PLEKHM1 mediate interaction with the small GTPase Rab7, which is found on late endosomes and autophagosomes. RH domains contain 16 conserved cysteine and histidine residues that bind zinc atoms and form at least 4 zinc finger motifs. Amino acid residues toward the C-terminus of the RH domain of Rubicon have been shown to be essential for interaction with Rab7. Structure The 3D atomic structure of the Rubicon RH domain in complex with Rab7 has been determined by X-ray crystallography. The structure of the RH domain has an "L" shape, with the base of the "L" making contact with the switch regions of Rab7. The st ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein Domain
In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of several domains, and a domain may appear in a variety of different proteins. Molecular evolution uses domains as building blocks and these may be recombined in different arrangements to create proteins with different functions. In general, domains vary in length from between about 50 amino acids up to 250 amino acids in length. The shortest domains, such as zinc fingers, are stabilized by metal ions or disulfide bridges. Domains often form functional units, such as the calcium-binding EF hand domain of calmodulin. Because they are independently stable, domains can be "swapped" by genetic engineering between one protein and another to make chimeric proteins. Background The concept of the domain was first proposed in 1973 by Wetlaufer aft ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
X-ray Crystallography
X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles and intensities of these diffracted beams, a crystallographer can produce a three-dimensional picture of the density of electrons within the crystal. From this electron density, the mean positions of the atoms in the crystal can be determined, as well as their chemical bonds, their crystallographic disorder, and various other information. Since many materials can form crystals—such as salts, metals, minerals, semiconductors, as well as various inorganic, organic, and biological molecules—X-ray crystallography has been fundamental in the development of many scientific fields. In its first decades of use, this method determined the size of atoms, the lengths and types of chemical bonds, and the atomic-scale differences among various mat ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PLEKHM3
Pleckstrin Homology domain containing Family M Member 3, or PLEKHM3, is the hypothetical protein that in humans is encoded by the ''PLEKHM3'' gene.: plekstrin homology domain containing family member 3 PLEKHM3 is also known as DAPR (differentiation associated protein), and Pleckstrin Homology Domain Containing Family M, Member 1-like. Gene PLEKHM3 is a valid, protein coding gene that is located on the minus strand of the q-arm of chromosome 2. Its exact location is 2q33.3. Its genomic mRNA length is 9,807 base pairs. Its genomic DNA length is 24.3 kilobases. It has 8 exons, 4 common splice forms. Protein PLEKHM3 contains a Plekstrin Homology domain and a C-terminal Rubicon Homology domain (RH domain). Rubicon homology domains of other proteins (e.g., Rubicon and PLEKHM1), have been shown to mediate interaction with the small GTPase Rab7. The RH domain domain is conserved in PLEKHM3 homologs as distant as the Nile Tilapia. The molecular weight of PLEKHM3 87.2 kilodalton ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pacer (protein)
Pacer (also known as Rubicon-like) is a protein that in humans is encoded by the RUBCNL gene. Pacer has been shown to increase cellular autophagy through regulation of PI3KC3. Pacer contains a Rubicon homology (RH) domain at its C-terminus, which mediates binding to small GTPase Rab7. This domain is shared with RH domain containing family members Rubicon and PLEKHM1. Whereas Pacer appears to upregulate autophagic activity, Rubicon is a negative regulator of autophagy Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re .... References Further reading * * * * * {{gene-13-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Osteopetrosis
Osteopetrosis, literally "stone bone", also known as marble bone disease or Albers-Schönberg disease, is an extremely rare Biological inheritance, inherited disease, disorder whereby the bones harden, becoming Density, denser, in contrast to more prevalent conditions like osteoporosis, in which the bones become less dense and more brittle, or osteomalacia, in which the bones soften. Osteopetrosis can cause bones to dissolve and break. It is one of the hereditary causes of osteosclerosis. It is considered to be the prototype of osteosclerosing dysplasias. The cause of the disease is understood to be malfunctioning osteoclasts and their inability to resorb bone. Although human osteopetrosis is a heterogeneous disorder encompassing different molecular lesions and a range of clinical features, all forms share a single pathogenic nexus in the osteoclast. The exact molecular defects or location of the mutations taking place are unknown. Osteopetrosis was first described in 1903, by Ger ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phosphatidylinositol 3-phosphate
Phosphatidylinositol 3-phosphate (PtdIns3''P'') is a phospholipid found in cell membranes that helps to recruit a range of proteins, many of which are involved in protein trafficking, to the membranes. It is the product of both the class II and III phosphoinositide 3-kinases (PI 3-kinases) activity on phosphatidylinositol. PtdIns3''P'' is dephosphorylated by the myotubularin family of phosphatases, on the D3 position of the inositol ring, and can be converted to PtdIns(3,5)''P''2 by the lipid kinase PIKfyve. Both FYVE domains and PX domains – found in proteins such as SNX1, HGS, and EEA1 – bind to PtdIns3''P''. The majority of PtdIns3''P'' appears to be constitutively synthesised by the class III PI 3-kinase, PIK3C3 (Vps34), at endocytic membranes. Class II PI 3-kinases also appear to synthesise PtdIns3''P'', their activity however appears to be regulated by a range of stimuli, including growth factors. This suggests that specific pools of PtdIns3''P'' may be s ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FYVE Domain
In molecular biology the FYVE zinc finger domain is named after the four cysteine-rich proteins: Fab 1 (yeast orthologue of PIKfyve), YOTB, Vac 1 (vesicle transport protein), and EEA1, in which it has been found. FYVE domains bind phosphatidylinositol 3-phosphate, in a way dependent on its metal ion coordination and basic amino acids. The FYVE domain inserts into cell membranes in a pH-dependent manner. The FYVE domain has been connected to vacuolar protein sorting and endosome function. Structure The FYVE domain is composed of two small beta hairpins (or zinc knuckles) followed by an alpha helix. The FYVE finger binds two zinc ions. The FYVE finger has eight potential zinc coordinating cysteine positions and is characterized by having basic amino acids around the cysteines. Many members of this family also include two histidines in a sequence motif: The FYVE finger is structurally similar to the RING domain and the PHD finger. Examples The following is a list of human prote ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Beta Sheet
The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet. A β-strand is a stretch of polypeptide chain typically 3 to 10 amino acids long with backbone in an extended conformation. The supramolecular association of β-sheets has been implicated in the formation of the fibrils and protein aggregates observed in amyloidosis, notably Alzheimer's disease. History The first β-sheet structure was proposed by William Astbury in the 1930s. He proposed the idea of hydrogen bonding between the peptide bonds of parallel or antiparallel extended β-strands. However, Astbury did not have the necessary data on the bond geometry of the amino acids in order to build accurate models, especially since he did not then know that the peptide bond was planar. A refined versi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Alpha Helix
The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues earlier along the protein sequence. The alpha helix is also called a classic Pauling–Corey–Branson α-helix. The name 3.613-helix is also used for this type of helix, denoting the average number of residues per helical turn, with 13 atoms being involved in the ring formed by the hydrogen bond. Among types of local structure in proteins, the α-helix is the most extreme and the most predictable from sequence, as well as the most prevalent. Discovery In the early 1930s, William Astbury showed that there were drastic changes in the X-ray fiber diffraction of moist wool or hair fibers upon significant stretching. The data suggested that the unstretched fibers had a coiled molecular structure with a characteristic repeat of ≈. Astb ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Zinc Finger
A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold. It was originally coined to describe the finger-like appearance of a hypothesized structure from the African clawed frog (''Xenopus laevis'') transcription factor IIIA. However, it has been found to encompass a wide variety of differing protein structures in eukaryotic cells. ''Xenopus laevis'' TFIIIA was originally demonstrated to contain zinc and require the metal for function in 1983, the first such reported zinc requirement for a gene regulatory protein followed soon thereafter by the Krüppel factor in ''Drosophila''. It often appears as a metal-binding domain in multi-domain proteins. Proteins that contain zinc fingers (zinc finger proteins) are classified into several different structural families. Unlike many other clearly defined supersecondary structures such as Greek keys or β hairpins, there are a number of t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Amino Acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha amino acids appear in the genetic code. Amino acids can be classified according to the locations of the core structural functional groups, as Alpha and beta carbon, alpha- , beta- , gamma- or delta- amino acids; other categories relate to Chemical polarity, polarity, ionization, and side chain group type (aliphatic, Open-chain compound, acyclic, aromatic, containing hydroxyl or sulfur, etc.). In the form of proteins, amino acid '' residues'' form the second-largest component (water being the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. It is thought that they played a key role in enabling life ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Histidine
Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the deprotonated –COO− form under biological conditions), and an imidazole side chain (which is partially protonated), classifying it as a positively charged amino acid at physiological pH. Initially thought essential only for infants, it has now been shown in longer-term studies to be essential for adults also. It is encoded by the codons CAU and CAC. Histidine was first isolated by Albrecht Kossel and Sven Gustaf Hedin in 1896. It is also a precursor to histamine, a vital inflammatory agent in immune responses. The acyl radical is histidyl. Properties of the imidazole side chain The conjugate acid (protonated form) of the imidazole side chain in histidine has a p''K''a of approximately 6.0. Thus, below a pH of 6, the imidazole ring ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
