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Structure of the mature Rous sarcoma virus lattice reveals a role for IP6 in the formation of the capsid hexamer.

<div class='caption-title'>Effect of IP6 on RSV in vitro and in cells.</div>
<div class='caption-title'>Cryo-electron tomography of RSV CASPNC CLPs assembled in the presence of IP6.</div>
<div class='caption-title'>Building blocks of the mature CASPNC lattice.</div>
Obr M, Ricana CL, Nikulin N, Feathers JR, Klanschnig M, Thader A, Johnson MC, Vogt VM, Schur FKM, Dick RA
OpenAccess logo Nat Commun 12 3226 (2021)

Cited: 11 times
EuropePMC logo PMID: 34050170

Abstract

Inositol hexakisphosphate (IP6) is an assembly cofactor for HIV-1. We report here that IP6 is also used for assembly of Rous sarcoma virus (RSV), a retrovirus from a different genus. IP6 is ~100-fold more potent at promoting RSV mature capsid protein (CA) assembly than observed for HIV-1 and removal of IP6 in cells reduces infectivity by 100-fold. Here, visualized by cryo-electron tomography and subtomogram averaging, mature capsid-like particles show an IP6-like density in the CA hexamer, coordinated by rings of six lysines and six arginines. Phosphate and IP6 have opposing effects on CA in vitro assembly, inducing formation of T = 1 icosahedrons and tubes, respectively, implying that phosphate promotes pentamer and IP6 hexamer formation. Subtomogram averaging and classification optimized for analysis of pleomorphic retrovirus particles reveal that the heterogeneity of mature RSV CA polyhedrons results from an unexpected, intrinsic CA hexamer flexibility. In contrast, the CA pentamer forms rigid units organizing the local architecture. These different features of hexamers and pentamers determine the structural mechanism to form CA polyhedrons of variable shape in mature RSV particles.

Reviews citing this publication (4)

  1. Structural Analysis of Retrovirus Assembly and Maturation. Krebs AS, Mendonça LM, Zhang P. Viruses 14 54 (2021)
  2. A Structural Perspective of the Role of IP6 in Immature and Mature Retroviral Assembly. Obr M, Schur FKM, Dick RA. Viruses 13 1853 (2021)
  3. Inositol Phosphates and Retroviral Assembly: A Cellular Perspective. Ricaña CL, Dick RA. Viruses 13 2516 (2021)
  4. Visualization of Retroviral Gag-Genomic RNA Cellular Interactions Leading to Genome Encapsidation and Viral Assembly: An Overview. Bernacchi S. Viruses 14 324 (2022)

Articles citing this publication (7)

  1. HIV-1 is dependent on its immature lattice to recruit IP6 for mature capsid assembly. Renner N, Kleinpeter A, Mallery DL, Albecka A, Rifat Faysal KM, Böcking T, Saiardi A, Freed EO, James LC. Nat Struct Mol Biol 30 370-382 (2023)
  2. Inositol Hexakisphosphate (IP6) Accelerates Immature HIV-1 Gag Protein Assembly toward Kinetically Trapped Morphologies. Pak AJ, Gupta M, Yeager M, Voth GA. J Am Chem Soc 144 10417-10428 (2022)
  3. Structure of a Ty1 restriction factor reveals the molecular basis of transposition copy number control. Cottee MA, Beckwith SL, Letham SC, Kim SJ, Young GR, Stoye JP, Garfinkel DJ, Taylor IA. Nat Commun 12 5590 (2021)
  4. High-affinity anti-Arc nanobodies provide tools for structural and functional studies. Markússon S, Hallin EI, Bustad HJ, Raasakka A, Xu J, Muruganandam G, Loris R, Martinez A, Bramham CR, Kursula P. PLoS One 17 e0269281 (2022)
  5. Molecular architecture and conservation of an immature human endogenous retrovirus. Krebs AS, Liu HF, Zhou Y, Rey JS, Levintov L, Shen J, Howe A, Perilla JR, Bartesaghi A, Zhang P. Nat Commun 14 5149 (2023)
  6. Nanobody-peptide-conjugate (NPC) for passive immunotherapy against SARS-CoV-2 variants of concern (VoC): a prospective pan-coronavirus therapeutics. Panda M, Kalita E, Singh S, Kumar K, Prajapati VK. Mol Divers 27 2577-2603 (2023)
  7. Structural insights into HIV-1 polyanion-dependent capsid lattice formation revealed by single particle cryo-EM. Highland CM, Tan A, Ricaña CL, Briggs JAG, Dick RA. Proc Natl Acad Sci U S A 120 e2220545120 (2023)


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