Structure of the immature HIV-1 capsid in intact virus particles at 8.8 Å resolution - PubMed (original) (raw)

Comparative Study

. 2015 Jan 22;517(7535):505-8.

doi: 10.1038/nature13838. Epub 2014 Nov 2.

Affiliations

• PMID: 25363765
• DOI: 10.1038/nature13838

Comparative Study

Structure of the immature HIV-1 capsid in intact virus particles at 8.8 Å resolution

Florian K M Schur et al. Nature. 2015.

Abstract

Human immunodeficiency virus type 1 (HIV-1) assembly proceeds in two stages. First, the 55 kilodalton viral Gag polyprotein assembles into a hexameric protein lattice at the plasma membrane of the infected cell, inducing budding and release of an immature particle. Second, Gag is cleaved by the viral protease, leading to internal rearrangement of the virus into the mature, infectious form. Immature and mature HIV-1 particles are heterogeneous in size and morphology, preventing high-resolution analysis of their protein arrangement in situ by conventional structural biology methods. Here we apply cryo-electron tomography and sub-tomogram averaging methods to resolve the structure of the capsid lattice within intact immature HIV-1 particles at subnanometre resolution, allowing unambiguous positioning of all α-helices. The resulting model reveals tertiary and quaternary structural interactions that mediate HIV-1 assembly. Strikingly, these interactions differ from those predicted by the current model based on in vitro-assembled arrays of Gag-derived proteins from Mason-Pfizer monkey virus. To validate this difference, we solve the structure of the capsid lattice within intact immature Mason-Pfizer monkey virus particles. Comparison with the immature HIV-1 structure reveals that retroviral capsid proteins, while having conserved tertiary structures, adopt different quaternary arrangements during virus assembly. The approach demonstrated here should be applicable to determine structures of other proteins at subnanometre resolution within heterogeneous environments.

PubMed Disclaimer

Similar articles

• The Structure of Immature Virus-Like Rous Sarcoma Virus Gag Particles Reveals a Structural Role for the p10 Domain in Assembly.
  Schur FK, Dick RA, Hagen WJ, Vogt VM, Briggs JA. Schur FK, et al. J Virol. 2015 Oct;89(20):10294-302. doi: 10.1128/JVI.01502-15. Epub 2015 Jul 29. J Virol. 2015. PMID: 26223638 Free PMC article.
• Cryo-electron microscopy of tubular arrays of HIV-1 Gag resolves structures essential for immature virus assembly.
  Bharat TA, Castillo Menendez LR, Hagen WJ, Lux V, Igonet S, Schorb M, Schur FK, Kräusslich HG, Briggs JA. Bharat TA, et al. Proc Natl Acad Sci U S A. 2014 Jun 3;111(22):8233-8. doi: 10.1073/pnas.1401455111. Epub 2014 May 19. Proc Natl Acad Sci U S A. 2014. PMID: 24843179 Free PMC article.
• Structure of the immature retroviral capsid at 8 Å resolution by cryo-electron microscopy.
  Bharat TA, Davey NE, Ulbrich P, Riches JD, de Marco A, Rumlova M, Sachse C, Ruml T, Briggs JA. Bharat TA, et al. Nature. 2012 Jul 19;487(7407):385-9. doi: 10.1038/nature11169. Nature. 2012. PMID: 22722831
• The molecular architecture of HIV.
  Briggs JA, Kräusslich HG. Briggs JA, et al. J Mol Biol. 2011 Jul 22;410(4):491-500. doi: 10.1016/j.jmb.2011.04.021. J Mol Biol. 2011. PMID: 21762795 Review.
• Molecular Architecture of the Retroviral Capsid.
  Perilla JR, Gronenborn AM. Perilla JR, et al. Trends Biochem Sci. 2016 May;41(5):410-420. doi: 10.1016/j.tibs.2016.02.009. Epub 2016 Mar 30. Trends Biochem Sci. 2016. PMID: 27039020 Free PMC article. Review.

Cited by

• Cryo-electron microscopy in the study of virus entry and infection.
  Dutta M, Acharya P. Dutta M, et al. Front Mol Biosci. 2024 Jul 24;11:1429180. doi: 10.3389/fmolb.2024.1429180. eCollection 2024. Front Mol Biosci. 2024. PMID: 39114367 Free PMC article. Review.
• Post-Translational Modifications of Retroviral HIV-1 Gag Precursors: An Overview of Their Biological Role.
  Bussienne C, Marquet R, Paillart JC, Bernacchi S. Bussienne C, et al. Int J Mol Sci. 2021 Mar 11;22(6):2871. doi: 10.3390/ijms22062871. Int J Mol Sci. 2021. PMID: 33799890 Free PMC article. Review.
• Helical Conformation in the CA-SP1 Junction of the Immature HIV-1 Lattice Determined from Solid-State NMR of Virus-like Particles.
  Bayro MJ, Ganser-Pornillos BK, Zadrozny KK, Yeager M, Tycko R. Bayro MJ, et al. J Am Chem Soc. 2016 Sep 21;138(37):12029-32. doi: 10.1021/jacs.6b07259. Epub 2016 Sep 7. J Am Chem Soc. 2016. PMID: 27593947 Free PMC article.
• The nuclear egress complex of Epstein-Barr virus buds membranes through an oligomerization-driven mechanism.
  Thorsen MK, Draganova EB, Heldwein EE. Thorsen MK, et al. PLoS Pathog. 2022 Jul 8;18(7):e1010623. doi: 10.1371/journal.ppat.1010623. eCollection 2022 Jul. PLoS Pathog. 2022. PMID: 35802751 Free PMC article.
• Human Immunodeficiency Virus Type 2 Capsid Protein Mutagenesis Reveals Amino Acid Residues Important for Virus Particle Assembly.
  Yang H, Talledge N, Arndt WG, Zhang W, Mansky LM. Yang H, et al. J Mol Biol. 2022 Oct 15;434(19):167753. doi: 10.1016/j.jmb.2022.167753. Epub 2022 Jul 19. J Mol Biol. 2022. PMID: 35868362 Free PMC article.

References

1. 1. Proc Natl Acad Sci U S A. 2005 Mar 29;102(13):4729-34 - PubMed
2. 1. Nature. 2012 Jul 19;487(7407):385-9 - PubMed
3. 1. Clin Ther. 2000 May;22(5):549-72 - PubMed
4. 1. J Mol Biol. 2003 Oct 31;333(4):721-45 - PubMed
5. 1. J Struct Biol. 2009 Dec;168(3):378-87 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Nature Publishing Group
  • Ovid Technologies, Inc.

• Other Literature Sources

  • The Lens - Patent Citations Database
  • scite Smart Citations