This domain family is found in eukaryotes, and is approximately 40 amino acids in length. This domain is the active domain of CEP55. CEP55 is a protein involved in cytokinesis, specifically in abscission of the plasma membrane at the midbody. To perform this function, CEP55 complexes with ESCRT-I (by a Proline rich sequence in its TSG101 domain) and ALIX. This is the domain on CEP55 which binds to both TSG101 and ALIX. It also acts as a hinge between the N and C termini. This domain is called EABR.
HIV protein p6 contains two late-budding domains (L domains) which are short sequence motifs essential for viral particle release. p6 interacts with the endosomal sorting complex and represents a docking site for several cellular and binding factors []. The PTAP motif interacts with the cellular budding factor TSG101 []. This domain is also found in some chimpanzee immunodeficiency virus (SIV-cpz) proteins.
Ebola virus sp. are non-segmented, negative-strand RNA viruses that causes severe haemorrhagic fever in humans with high rates of mortality. The virus matrix protein VP40 is a major structural protein that plays a central role in virus assembly and budding at the plasma membrane of infected cells. VP40 proteins associate with cellular membranes, interact with the cytoplasmic tails of glycoproteins, and bind to the ribonucleoprotein complex. The VP40 monomer consists of two domains, the N-terminal oligomerization domain and the C-terminal membrane-binding domain, connected by a flexible linker. Both the N- and C-terminal domains fold into beta sandwich structures of similar topology []. Within the N-terminal domain are two overlapping L-domains with the sequences PTAP and PPEY at residues 7 to13, which are required for efficient budding []. L-domains are thought to mediate their function in budding through their interaction with specific host cellular proteins, such as tsg101 and vps-4 []. This entry represents the N- and C-terminal domains of the VP40 matrix protein.
Ebola virus sp. are non-segmented, negative-strand RNA viruses that causes severe haemorrhagic fever in humans with high rates of mortality. The virus matrix protein VP40 is a major structural protein that plays a central role in virus assembly and budding at the plasma membrane of infected cells. VP40 proteins associate with cellular membranes, interact with the cytoplasmic tails of glycoproteins, and bind to the ribonucleoprotein complex. The VP40 monomer consists of two domains, the N-terminal oligomerization domain and the C-terminal membrane-binding domain, connected by a flexible linker. Both the N- and C-terminal domains fold into beta sandwich structures of similar topology []. Within the N-terminal domain are two overlapping L-domains with the sequences PTAP and PPEY at residues 7 to13, which are required for efficient budding []. L-domains are thought to mediate their function in budding through their interaction with specific host cellular proteins, such as tsg101 and vps-4 []. This entry describes the VP40 C-terminal domain.
Ebola virus sp. are non-segmented, negative-strand RNA viruses that causes severe haemorrhagic fever in humans with high rates of mortality. The virus matrix protein VP40 is a major structural protein that plays a central role in virus assembly and budding at the plasma membrane of infected cells. VP40 proteins associate with cellular membranes, interact with the cytoplasmic tails of glycoproteins, and bind to the ribonucleoprotein complex. The VP40 monomer consists of two domains, the N-terminal oligomerization domain and the C-terminal membrane-binding domain, connected by a flexible linker. Both the N- and C-terminal domains fold into beta sandwich structures of similar topology []. Within the N-terminal domain are two overlapping L-domains with the sequences PTAP and PPEY at residues 7 to13, which are required for efficient budding []. L-domains are thought to mediate their function in budding through their interaction with specific host cellular proteins, such as tsg101 and vps-4 [].
Ebola virus sp. are non-segmented, negative-strand RNA viruses that causes severe haemorrhagic fever in humans with high rates of mortality. The virus matrix protein VP40 is a major structural protein that plays a central role in virus assembly and budding at the plasma membrane of infected cells. VP40 proteins associate with cellular membranes, interact with the cytoplasmic tails of glycoproteins, and bind to the ribonucleoprotein complex. The VP40 monomer consists of two domains, the N-terminal oligomerization domain and the C-terminal membrane-binding domain, connected by a flexible linker. Both the N- and C-terminal domains fold into beta sandwich structures of similar topology []. Within the N-terminal domain are two overlapping L-domains with the sequences PTAP and PPEY at residues 7 to13, which are required for efficient budding []. L-domains are thought to mediate their function in budding through their interaction with specific host cellular proteins, such as tsg101 and vps-4 []. This entry describes the VP40 N-terminal domain. It is the region of the protein where the two VP40 monomers bind.
The N-terminal ubiquitin E2 variant (UEV) domain is ~145 amino acid residues in length and shows significant sequence similarity to E2 ubiquitin ligases but is unable to catalyze ubiquitin transfer as it lacks the active site cysteine that forms the transient thioester bond with the C terminus of ubiquitin (Ub). Nevertheless, at least some UEVs have retained the ability to bind Ub, and appear to act either as cofactors in ubiquitylation reactions, or as ubiquitin sensors. UEV domains also frequently contain other protein recognition motifs, and may generally serve to couple protein and Ub binding functions to facilitate the formation of multiprotein complexes [, , , ]. The UEV domain consists of a twisted four-stranded antiparallel β-sheet having a meander topology, with four α-helices packed against one face of the sheet. The UEV fold is generally similar to canonical E2 ligases in the hydrophobic core and 'active site' regions, but differs significantly at both its N- and C-termini [, ]. The UEV domain is found in the eukaryotic tumour susceptibility gene 101 protein (TSG101). Altered transcripts of this gene have been detected in sporadic breast cancers and many other Homo sapiens malignancies. However, the involvement of this gene in neoplastic transformation and tumourigenesis is still elusive. TSG101 is required for normal cell function of embryonic and adult tissues but this gene is not a tumour suppressor for sporadic forms of breast cancer [].
Tom1 (target of Myb 1) and its related proteins (Tom1L1 and Tom1L2) constitute a protein family and share an N-terminal VHS (Vps27p/Hrs/Stam) domain followed by a GAT (GGA and Tom1) domain.VHS domains are found at the N termini of select proteins involved in intracellular membrane trafficking and are often localized to membranes. The three dimensional structure of human TOM1 VHS domain reveals eight helices arranged in a superhelix. The surface of the domain has two main features: (1) a basic patch on one side due to several conserved positively charged residues on helix 3 and (2) a negatively charged ridge on the opposite side, formed by residues on helix 2 []. The basic patch is thought to mediate membrane binding.It was demonstrated that the GAT domain of both Tom1 and Tom1L1 binds ubiquitin, suggesting that these proteins might participate in the sorting of ubiquitinated proteins into multivesicular bodies (MVB) []. Moreover, Tom1L1 interacts with members of the MVB sorting machinery. Specifically, the VHS domain of Tom1L1 interacts with Hrs (hepatocyte growth factor-regulated tyrosine kinase substrate), whereas a PTAP motif, located between the VHS and GAT domains of Tom1L1, is responsible for binding to TSG101 (tumour susceptibility gene 101). Myc epitope-tagged Tom1L1 is recruited to endosomes following Hrs expression. In addition, Tom1L1 possesses several tyrosine motifs at the C-terminal region that mediate interactions with members of the Src family kinases and other signalling proteins such as Grb2 and p85. Expression of a constitutively active form of Fyn kinase promotes the recruitment of Tom1L1 to enlarged endosomes. It is proposed that Tom1L1 could act as an intermediary between the signalling and degradative pathways [].Over expression of Tom1 suppresses activation of the transcription factors NF-kappaB and AP-1, induced by either IL-1beta or tumour necrosis factor (TNF)-alpha, and the VHS domain of Tom1 is indispensable for this suppressive activity. This suggests that Tom1 is a common negative regulator of signalling pathways induced by IL-1beta and TNF-alpha [].
