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141  structures 166  species 0  interactions 40495  sequences 17  architectures

Family: GP41 (PF00517)

Summary: Retroviral envelope protein

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This is the Wikipedia entry entitled "Gp41". More...

Gp41 Edit Wikipedia article

GP41
PDB 1f23 EBI.jpg
Example crystal structures of HIV-1 envelope glycoprotein Gp41
Identifiers
Symbol GP41
Pfam PF00517
InterPro IPR000328
SCOP 2siv
SUPERFAMILY 2siv

Gp41 also known as glycoprotein 41 is a subunit of the envelope protein complex of retroviruses, including Human immunodeficiency virus (HIV). Gp41 is a transmembrane protein that contains several sites within its ectodomain that are required for infection of host cells.

Gene and post-translational modifications[edit]

The env gene codes for gp160, a precursor, which is extensively glycosylated and proteolytically cleaved into two subunits gp120 and gp41 (this protein) by furin, a host cellular protease.

Function[edit]

In a free virion, the fusion peptides at the amino termini of gp41 are buried within the envelope complex in an inactive non-fusogengic state that is stabilized by a non-covalent bond with gp120. Gp120 binds to a CD4 and a co-receptor (CCR5 or CXCR4), found on susceptible cells such as Helper T cells and macrophages.[1] As a result, a cascade of conformational changes occurs in the gp120 and gp41 proteins. The core of gp41 folds into a six helical bundle structure exposing the previously hidden gp41 fusion peptides which then assist in the fusion with the host cell.[2] The activation process occurs readily which suggest that the inactive state of gp41 is metastable and the conformational changes allow gp41 to achieve its more stable active state.

As a drug target[edit]

The interaction of gp41 fusion peptides with the target cell causes a formation of an intermediate, pre-hairpin structure which bridges and fuses the viral and host membranes together. The pre-hairpin structure has a relatively long half-life which makes it a target for therapeutic intervention and inhibitory peptides.[3]

Enfuvirtide (also known as T-20) is a fusion inhibitor drug that binds to the pre-hairpin structure and prevents membrane fusion and HIV-1 entry to the cell. The vulnerability of this structure has initiated development towards a whole spectrum of fusion preventing drugs.[4] A variety of naturally-occurring molecules have also been shown to bind gp41 and prevent HIV-1 entry. [5]

References[edit]

  1. ^ Chan DC, Kim PS (May 1998). "HIV entry and its inhibition". Cell 93 (5): 681–4. doi:10.1016/S0092-8674(00)81430-0. PMID 9630213. 
  2. ^ Buzon V, Natrajan G, Schibli D, Campelo F, Kozlov MM, Weissenhorn W (May 2010). "Crystal structure of HIV-1 gp41 including both fusion peptide and membrane proximal external regions". PLoS Pathog. 6 (5): e1000880. doi:10.1371/journal.ppat.1000880. PMC 2865522. PMID 20463810. 
  3. ^ Lalezari JP, Henry K, O'Hearn M, Montaner JS, Piliero PJ, Trottier B, Walmsley S, Cohen C, Kuritzkes DR, Eron JJ, Chung J, DeMasi R, Donatacci L, Drobnes C, Delehanty J, Salgo M (May 2003). "Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America". N. Engl. J. Med. 348 (22): 2175–85. doi:10.1056/NEJMoa035026. PMID 12637625. 
  4. ^ Root MJ, Steger HK (2004). "HIV-1 gp41 as a target for viral entry inhibition". Curr. Pharm. Des. 10 (15): 1805–25. doi:10.2174/1381612043384448. PMID 15180542. 
  5. ^ Eade CR, Wood MP, Cole AM (2012). "Mechanisms and modifications of naturally occurring host defense peptides for anti-HIV microbicide development.". Curr. HIV. Res. 10 (1): 61–72. doi:10.2174/157016212799304580. PMID 22264047. 

External links[edit]

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.

Retroviral envelope protein Provide feedback

This family includes envelope protein from a variety of retroviruses. It includes the GP41 subunit of the envelope protein complex from human and simian immunodeficiency viruses (HIV and SIV) which mediate membrane fusion during viral entry. The family also includes bovine immunodeficiency virus, feline immunodeficiency virus and Equine infectious anaemia (EIAV). The family also includes the Gp36 protein from mouse mammary tumour virus (MMTV) and human endogenous retroviruses (HERVs).

Literature references

  1. Malashkevich VN, Chan DC, Chutkowski CT, Kim PS; , Proc Natl Acad Sci USA 1998;95:9134-9139.: Crystal structure of the simian immunodeficiency virus (SIV) gp41 core: conserved helical interactions underlie the broad inhibitory activity of gp41 peptides. PUBMED:9689046 EPMC:9689046


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000328

This entry represents envelope proteins from a variety of retroviruses. It includes the GP41 subunit of the envelope protein complex from Human immunodeficiency virus (HIV) and Simian-Human immunodeficiency virus (SIV), which mediate membrane fusion during viral entry [PUBMED:9689046]. It has a core composed of a six-helix bundle and is folded by its trimeric N- and C-terminal heptad-repeats (NHR and CHR) [PUBMED:18417584]. Derivatives of this protein prevent HIV-1 from entering cell lines and primary human CD4+ cells in vitro [PUBMED:18449216], making it an attractive subject of gene therapy studies against HIV and related retroviruses.

The entry also represents envelop proteins from Bovine immunodeficiency virus, Feline immunodeficiency virus and Equine infectious anemia virus (EIAV) [PUBMED:2841805, PUBMED:10790112], as well as the Gp36 protein from Mouse mammary tumor virus (MMTV) and Human endogenous retrovirus (HERV).

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

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Alignments

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(23)
Full
(40495)
Representative proteomes NCBI
(37279)
Meta
(0)
RP15
(12)
RP35
(12)
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RP75
(21)
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  Seed
(23)
Full
(40495)
Representative proteomes NCBI
(37279)
Meta
(0)
RP15
(12)
RP35
(12)
RP55
(12)
RP75
(21)
Alignment:
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  Seed
(23)
Full
(40495)
Representative proteomes NCBI
(37279)
Meta
(0)
RP15
(12)
RP35
(12)
RP55
(12)
RP75
(21)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

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Seed source: Pfam-B_44 (release 1.0)
Previous IDs: none
Type: Family
Author: Finn RD, Bateman A
Number in seed: 23
Number in full: 40495
Average length of the domain: 171.40 aa
Average identity of full alignment: 74 %
Average coverage of the sequence by the domain: 29.32 %

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 25.1 25.1
Trusted cut-off 25.1 25.3
Noise cut-off 25.0 25.0
Model length: 204
Family (HMM) version: 12
Download: download the raw HMM for this family

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 GP41 domain has been found. There are 141 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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