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4  structures 20  species 0  interactions 35  sequences 1  architecture

Family: VP40 (PF07447)

Summary: Matrix protein VP40

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Vp40 protein domain Edit Wikipedia article

VP40
PDB 1es6 EBI.jpg
crystal structure of the matrix protein of ebola virus
Identifiers
Symbol VP40
Pfam PF07447
InterPro IPR008986
SCOP 1h2c
SUPERFAMILY 1h2c

In molecular biology, this entry is about a Viral matrix Protein named VP40. Most commonly, it is found in the Ebola virus (EBOV). This virus is a type of non-segmented, negative-strand RNA virus. They cause severe haemorrhagic fever in humans with high rates of mortality, therefore they are lethal. 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 work by associating with cellular membranes, interacting with the cytoplasmic tails of glycoproteins, and binding to the ribonucleoprotein complex.

Structure[edit]

The VP40 monomer consists of two protein domains, the N-terminal oligomerization protein 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.[1] 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.[2] L-domains are thought to mediate their function in budding through their interaction with specific host cellular proteins, such as tsg101 and vps-4.[3]

Function[edit]

The matrix protein VP40 coordinates numerous functions in the viral life cycle of the Ebola virus. These include:regulation of viral transcription, morphogenesis, packaging and budding of mature virions. VP40 goes through intermediate states of assembly (e.g. octamers). It has been noted that proteins encoded by EBOV (VP30, VP35, and VP40) act independently as suppressors of RNA silencing, indicating that the virus actively resists cellular RNAi during replication.[4]

The significance of EBOV[edit]

Studying about the matrix protein VP40 is important since the Ebola virus has been considered a Category A Bioterrorism agent. Additionally, in humans and other organisms EBOV has been known to cause a lethal haemorrhagic fever. Expression of the matrix protein VP40 is sufficient to generate VLP’s in a mammalian host that are remarkably indistinguishable from live virus, from a morphological standpoint[4]

References[edit]

  1. ^ Dessen A, Volchkov V, Dolnik O, Klenk HD, Weissenhorn W (August 2000). "Crystal structure of the matrix protein VP40 from Ebola virus". EMBO J. 19 (16): 4228–36. doi:10.1093/emboj/19.16.4228. PMC 302032. PMID 10944105. 
  2. ^ Timmins J, Schoehn G, Ricard-Blum S, Scianimanico S, Vernet T, Ruigrok RW, Weissenhorn W (February 2003). "Ebola virus matrix protein VP40 interaction with human cellular factors Tsg101 and Nedd4". J. Mol. Biol. 326 (2): 493–502. doi:10.1016/S0022-2836(02)01406-7. PMID 12559917. 
  3. ^ Licata JM, Simpson-Holley M, Wright NT, Han Z, Paragas J, Harty RN (February 2003). "Overlapping motifs (PTAP and PPEY) within the Ebola virus VP40 protein function independently as late budding domains: involvement of host proteins TSG101 and VPS-4". J. Virol. 77 (3): 1812–9. PMC 140960. PMID 12525615. 
  4. ^ a b Silva LP, Vanzile M, Bavari S, Aman JM, Schriemer DC (2012). "Assembly of Ebola Virus Matrix Protein VP40 Is Regulated by Latch-Like Properties of N and C Terminal Tails.". PLoS ONE 7 (7): e39978. doi:10.1371/journal.pone.0039978. PMC 3390324. PMID 22792204. 

This article incorporates text from the public domain Pfam and InterPro IPR008986

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Matrix protein VP40 Provide feedback

This family contains viral VP40 matrix proteins that seem to be restricted to the Filoviridae. These play an important role in the assembly process of virus particles by interacting with cellular factors, cellular membranes, and the ribonuclearprotein particle complex. It has been shown that the N-terminal region of VP40 folds into a mixture of hexameric and octameric states - these may have distinct roles [1].

Literature references

  1. Timmins J, Schoehn G, Kohlhaas C, Klenk HD, Ruigrok RW, Weissenhorn W; , Virology 2003;312:359-368.: Oligomerization and polymerization of the filovirus matrix protein VP40. PUBMED:12919741 EPMC:12919741


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR008986

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 [PUBMED:10944105]. 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 [PUBMED:12559917]. L-domains are thought to mediate their function in budding through their interaction with specific host cellular proteins, such as tsg101 and vps-4 [PUBMED:12525615].

Domain organisation

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Alignments

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RP55
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Representative proteomes NCBI
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External links

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Curation View help on the curation process

Seed source: Pfam-B_22295 (release 10.0)
Previous IDs: none
Type: Family
Author: Vella Briffa B
Number in seed: 2
Number in full: 35
Average length of the domain: 287.30 aa
Average identity of full alignment: 60 %
Average coverage of the sequence by the domain: 91.60 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 307.4 307.0
Noise cut-off 17.3 16.4
Model length: 295
Family (HMM) version: 7
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Species distribution

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the VP40 domain has been found. There are 4 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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