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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

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

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

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

^ 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.
^ 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.
^ 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.
^ 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.
^ 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

gp41 Envelope Protein, HIV at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 妊娠時の抗レトロウイルス剤：侵入阻害剤およびインテグラーゼ阻害剤 antiretroviral medications in pregnancy entry and integrase inhibitors
2. HIV関連神経障害の疫学、病因および臨床症状 epidemiology pathogenesis and clinical features of hiv associated neuropathies
3. ヒト免疫不全ウイルスと透析 human immunodeficiency virus and dialysis
4. 治療経験のある薬剤耐性HIV感染患者における抗レトロウイルス療法の選択 selection of antiretroviral therapy for the treatment experienced patient with drug resistant hiv infection

English Journal

Helical peptide arrays for lead identification and interaction site mapping.

Langedijk JP, Zekveld MJ, Ruiter M, Corti D, Back JW.SourcePepscan Therapeutics, 8243 RC Lelystad, The Netherlands.
Analytical biochemistry.Anal Biochem.2011 Oct 1;417(1):149-55. Epub 2011 Jun 12.
Libraries composed of linear and cyclic peptides cannot fully represent the higher order structures of most antigenic sites. To map the binding site of ligands or antibodies, a larger part of the three-dimensional space should be sampled. Because parallel synthesis of large arrays of peptides on hyd
PMID 21708118

Japanese Journal

ペプチドミメティックによる創薬研究

鳴海哲夫,糸谷恭子,玉村啓和
生体材料工学研究所年報 44, 3-6, 2010
NAID 40018820671

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★リンクテーブル★

リンク元	「ヒト免疫不全ウイルス」
拡張検索	「HIV envelope protein gp41」「HIVエンベロープタンパク質gp41」「エイズウイルス外膜タンパク質gp41」
関連記事	「gp」

「ヒト免疫不全ウイルス」

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

GP41
	Example crystal structures of HIV-1 envelope glycoprotein Gp41
Identifiers
Symbol	GP41
Pfam	PF00517
InterPro	IPR000328
SCOP	2siv
SUPERFAMILY	2siv
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary