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Structure of Human Immunodeficiency Virus hexameric capsid PDB:3H47

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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).[2] [3]
  • Cyclophylin A [4]
  • 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

Cristal structure of PF-3450074 with N terminal domain of HIV capsid PDB:2XDE

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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

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

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