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From Proteopedia

Revision as of 09:10, 28 January 2016

Introduction

Function

Chat.^[1]

Structural highlights

As you can see on the figure bellow, each monomer of capsid is linked to five others to form a hexamer. These hexamers (approximately 330 per virus) associates themselves to form a non-symetrical protein complex.

Interactions with others partners

Even if p24 is classified as a structural protein, it is also involved in many cellular infection processes.

You can find bellow in a non exhaustive list of p24 partners :

• Cytoskeleton (MAP1A, MAP1S, CKAP1, WIRE)
• Cyclophylin A
• Nuclear pore (certainly but not sure)
• Dynein
• Integrase ?

The HIV-1 capsid acts like a kind of "nuclear localisation signal" because it targets directly the virus toward the nucleus, where the integration takes place.

Capsid as therapeutical target

Thank to its central role in viral infectious process (genome protection, enveloppe cohesion, uncoating, budding), HIV capsid is a very good target for antiviral drugs. As a result, many research teams are working in this way and some molecules such as PF-3450074 are very promising. By binding to a "central pocket" on P24, it was shown in vitro that this compound is inhibiting the new viruses assembly, and consequently the virus budding.

References

1. ↑ Uniprot

Structural image : By Thomas Splettstoesser (www.scistyle.com) (Own work) [CC BY-SA 4.0 (http://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons

Cytoskeleton interactions :

Fernandez J, Gärtner K, Becker A, et al. HIV-1 capsid interacts with cytoskeletal-associated proteins for intracytoplasmic routing to the nucleus. Retrovirology. 2013;10(Suppl 1):P34. doi:10.1186/1742-4690-10-S1-P34.^[1]

- Fernandez J, Portilho DM, Danckaert A, Munier S, Becker A, Roux P, Zambo A, Shorte S, Jacob Y, Vidalain PO, Charneau P, Clavel F, Arhel NJ. Microtubule-associated proteins 1 (MAP1) promote human immunodeficiency virus type I (HIV-1) intracytoplasmic routing to the nucleus. J Biol Chem. 2015 Feb 20;290(8):4631-46. doi: 10.1074/jbc.M114.613133. Epub 2014 Dec 11.

Cyclophylin A interaction :

- Marisa S. Briones, Charles W. Dobard and Samson A. Chow. Role of Human Immunodeficiency Virus Type 1 Integrase in Uncoating of the Viral Core. Accepted manuscript posted online 10 March 2010, doi:.1128/JVI.02382-09 J. Virol. May 2010 vol. 84 no. 10 5181-5190

Nuclear import :

HIV-1 capsid: the multifaceted key player in HIV-1 infection Nature Reviews Microbiology 13,471–483 (2015)doi:10.1038/nrmicro3503

Capsid targeting drug

Edward M. Campbell & Thomas J. Hope. HIV-1 capsid: the multifaceted key player in HIV-1 infection Nature Reviews Microbiology 13,471–483 (2015)doi:10.1038/nrmicro3503 Published online 16 July 2015