Home LiteratureArticle Details
PMID: 17396149 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Electron cryotomography of immature HIV-1 virions reveals the structure of the CA and SP1 Gag shells.

The EMBO journal ·Vol. 26 ·No. 8 ·2007-04-18 ·Pages 2218-26

Wright ER, Schooler JB, Ding HJ, Kieffer C, Fillmore C, Sundquist WI, Jensen GJ

Abstract

The major structural elements of retroviruses are contained in a single polyprotein, Gag, which in human immunodeficiency virus type 1 (HIV-1) comprises the MA, CA, spacer peptide 1 (SP1), NC, SP2, and p6 polypeptides. In the immature HIV-1 virion, the domains of Gag are arranged radially with the N-terminal MA domain at the membrane and C-terminal NC-SP2-p6 region nearest to the center. Here, we report the three-dimensional structures of individual immature HIV-1 virions, as obtained by electron cryotomography. The concentric shells of the Gag polyprotein are clearly visible, and radial projections of the different Gag layers reveal patches of hexagonal order within the CA and SP1 shells. Averaging well-ordered unit cells leads to a model in which each CA hexamer is stabilized by a bundle of six SP1 helices. This model suggests why the SP1 spacer is essential for assembly of the Gag lattice and how cleavage between SP1 and CA acts as a structural switch controlling maturation.

MeSH Terms
Capsid Proteins/chemistry Gene Products, gag/chemistry HIV-1/ultrastructure Models, Molecular Peptides/chemistry Tomography/methods Virion/ultrastructure
Chemicals
Capsid Proteins Gene Products, gag Peptides
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Wright Elizabeth R
Division of Biology, California Institute of Technology, Pasadena, CA, USA.
Schooler Jordan B
Ding H Jane
Kieffer Collin
Fillmore Christopher
Sundquist Wesley I
Jensen Grant J
References (57)
57 references, click to expand
  1. A conformational switch controlling HIV-1 morphogenesis.
    EMBO J. 2000 Jan 4;19(1):103-13 PMID: 10619849
  2. PA-457: a potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processing.
    Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13555-60 PMID: 14573704
  3. Efficient particle production by minimal Gag constructs which retain the carboxy-terminal domain of human immunodeficiency virus type 1 capsid-p2 and a late assembly domain.
    J Virol. 2000 Jun;74(12):5395-402 PMID: 10823843
  4. Mapping and characterization of the N-terminal I domain of human immunodeficiency virus type 1 Pr55(Gag).
    J Virol. 2000 Aug;74(16):7238-49 PMID: 10906178
  5. Evidence for a stable interaction of gp41 with Pr55(Gag) in immature human immunodeficiency virus type 1 particles.
    J Virol. 2000 Oct;74(20):9381-7 PMID: 11000206
  6. Image reconstructions of helical assemblies of the HIV-1 CA protein.
    Nature. 2000 Sep 21;407(6802):409-13 PMID: 11014200
  7. Organization of immature human immunodeficiency virus type 1.
    J Virol. 2001 Jan;75(2):759-71 PMID: 11134289
  8. Anti-human immunodeficiency virus activity of YK-FH312 (a betulinic acid derivative), a novel compound blocking viral maturation.
    Antimicrob Agents Chemother. 2001 Apr;45(4):1225-30 PMID: 11257038
  9. Modulation of HIV-like particle assembly in vitro by inositol phosphates.
    Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10875-9 PMID: 11526217
  10. Structure of the N-terminal 283-residue fragment of the immature HIV-1 Gag polyprotein.
    Nat Struct Biol. 2002 Jul;9(7):537-43 PMID: 12032547
  11. Characterization of a putative alpha-helix across the capsid-SP1 boundary that is critical for the multimerization of human immunodeficiency virus type 1 gag.
    J Virol. 2002 Nov;76(22):11729-37 PMID: 12388733
  12. Important role for the CA-NC spacer region in the assembly of bovine immunodeficiency virus Gag protein.
    J Virol. 2004 Jan;78(2):551-60 PMID: 14694086
  13. Small-molecule inhibition of human immunodeficiency virus type 1 replication by specific targeting of the final step of virion maturation.
    J Virol. 2004 Jan;78(2):922-9 PMID: 14694123
  14. Assembly properties of the human immunodeficiency virus type 1 CA protein.
    J Virol. 2004 Mar;78(5):2545-52 PMID: 14963157
  15. An improved strategy for automated electron microscopic tomography.
    J Struct Biol. 2004 Aug;147(2):91-101 PMID: 15193638
  16. The stoichiometry of Gag protein in HIV-1.
    Nat Struct Mol Biol. 2004 Jul;11(7):672-5 PMID: 15208690
  17. UCSF Chimera--a visualization system for exploratory research and analysis.
    J Comput Chem. 2004 Oct;25(13):1605-12 PMID: 15264254
  18. Flexibility in the P2 domain of the HIV-1 Gag polyprotein.
    Protein Sci. 2004 Aug;13(8):2101-7 PMID: 15238640
  19. High-resolution structure of a retroviral capsid hexameric amino-terminal domain.
    Nature. 2004 Sep 23;431(7007):481-5 PMID: 15386017
  20. Necessity of the spacer peptide between CA and NC in the Rous sarcoma virus gag protein.
    J Virol. 1993 Oct;67(10):6246-52 PMID: 8396679
  21. Three-dimensional structure of the human immunodeficiency virus type 1 matrix protein.
    J Mol Biol. 1994 Nov 25;244(2):198-223 PMID: 7966331
  22. The spacer peptide between human immunodeficiency virus capsid and nucleocapsid proteins is essential for ordered assembly and viral infectivity.
    J Virol. 1995 Jun;69(6):3407-19 PMID: 7745687
  23. Crystal structures of the trimeric human immunodeficiency virus type 1 matrix protein: implications for membrane association and assembly.
    Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3099-104 PMID: 8610175
  24. Computer visualization of three-dimensional image data using IMOD.
    J Struct Biol. 1996 Jan-Feb;116(1):71-6 PMID: 8742726
  25. The retroviral capsid domain dictates virion size, morphology, and coassembly of gag into virus-like particles.
    J Virol. 2005 Nov;79(21):13463-72 PMID: 16227267
  26. Analysis of human immunodeficiency virus type 1 Gag dimerization-induced assembly.
    J Virol. 2005 Dec;79(23):14498-506 PMID: 16282449
  27. Cryo-electron microscopy reveals conserved and divergent features of gag packing in immature particles of Rous sarcoma virus and human immunodeficiency virus.
    J Mol Biol. 2006 Jan 6;355(1):157-68 PMID: 16289202
  28. Inhibition of HIV-1 maturation via drug association with the viral Gag protein in immature HIV-1 particles.
    J Biol Chem. 2005 Dec 23;280(51):42149-55 PMID: 16251182
  29. Late budding domains and host proteins in enveloped virus release.
    Virology. 2006 Jan 5;344(1):55-63 PMID: 16364736
  30. The mechanism of HIV-1 core assembly: insights from three-dimensional reconstructions of authentic virions.
    Structure. 2006 Jan;14(1):15-20 PMID: 16407061
  31. Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly.
    Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11364-9 PMID: 16840558
  32. Implications for viral capsid assembly from crystal structures of HIV-1 Gag(1-278) and CA(N)(133-278).
    Biochemistry. 2006 Sep 26;45(38):11257-66 PMID: 16981686
  33. The morphology of the immature HIV-1 virion.
    Virology. 1997 Feb 3;228(1):112-4 PMID: 9024816
  34. Structure of the carboxyl-terminal dimerization domain of the HIV-1 capsid protein.
    Science. 1997 Oct 31;278(5339):849-53 PMID: 9346481
  35. Cryo-electron microscopy reveals ordered domains in the immature HIV-1 particle.
    Curr Biol. 1997 Oct 1;7(10):729-38 PMID: 9368755
  36. Analysis of the assembly function of the human immunodeficiency virus type 1 gag protein nucleocapsid domain.
    J Virol. 1998 Mar;72(3):1782-9 PMID: 9499028
  37. A putative alpha-helical structure which overlaps the capsid-p2 boundary in the human immunodeficiency virus type 1 Gag precursor is crucial for viral particle assembly.
    J Virol. 1998 Mar;72(3):2072-8 PMID: 9499062
  38. Proteolytic refolding of the HIV-1 capsid protein amino-terminus facilitates viral core assembly.
    EMBO J. 1998 Mar 16;17(6):1555-68 PMID: 9501077
  39. Efficient HIV-1 replication can occur in the absence of the viral matrix protein.
    EMBO J. 1998 May 1;17(9):2699-708 PMID: 9564051
  40. Morphopoietic determinants of HIV-1 Gag particles assembled in baculovirus-infected cells.
    Virology. 1998 Aug 1;247(2):160-9 PMID: 9705909
  41. The C-terminal half of the human immunodeficiency virus type 1 Gag precursor is sufficient for efficient particle assembly.
    J Virol. 1998 Nov;72(11):9313-7 PMID: 9765481
  42. HIV-1 gag proteins: diverse functions in the virus life cycle.
    Virology. 1998 Nov 10;251(1):1-15 PMID: 9813197
  43. Further evidence for hexagonal organization of HIV gag protein in prebudding assemblies and immature virus-like particles.
    J Struct Biol. 1998 Oct;123(2):143-9 PMID: 9843668
  44. Structures of the HIV-1 capsid protein dimerization domain at 2.6 A resolution.
    Acta Crystallogr D Biol Crystallogr. 1999 Jan;55(Pt 1):85-92 PMID: 10089398
  45. Mammalian SCAN domain dimer is a domain-swapped homolog of the HIV capsid C-terminal domain.
    Mol Cell. 2005 Jan 7;17(1):137-43 PMID: 15629724
  46. Betulinic acid derivatives as HIV-1 antivirals.
    Trends Mol Med. 2005 Jan;11(1):31-6 PMID: 15649820
  47. Helical structure determined by NMR of the HIV-1 (345-392)Gag sequence, surrounding p2: implications for particle assembly and RNA packaging.
    Protein Sci. 2005 Feb;14(2):375-86 PMID: 15659370
  48. Three-dimensional structure of HIV-1 virus-like particles by electron cryotomography.
    J Mol Biol. 2005 Feb 18;346(2):577-88 PMID: 15670606
  49. Assembly of human immunodeficiency virus precursor gag proteins.
    J Biol Chem. 2005 May 6;280(18):17664-70 PMID: 15734744
  50. Structural studies by electron tomography: from cells to molecules.
    Annu Rev Biochem. 2005;74:833-65 PMID: 15952904
  51. The discovery of a class of novel HIV-1 maturation inhibitors and their potential in the therapy of HIV.
    Expert Opin Investig Drugs. 2005 Jun;14(6):681-93 PMID: 16004596
  52. How retroviruses select their genomes.
    Nat Rev Microbiol. 2005 Aug;3(8):643-55 PMID: 16064056
  53. Role of lipid rafts in virus replication.
    Adv Virus Res. 2005;64:311-58 PMID: 16139599
  54. Retrovirus capsid protein assembly arrangements.
    J Mol Biol. 2003 Jan 3;325(1):225-37 PMID: 12473464
  55. Structural organization of authentic, mature HIV-1 virions and cores.
    EMBO J. 2003 Apr 1;22(7):1707-15 PMID: 12660176
  56. Functional surfaces of the human immunodeficiency virus type 1 capsid protein.
    J Virol. 2003 May;77(9):5439-50 PMID: 12692245
  57. Basic residues in human immunodeficiency virus type 1 nucleocapsid promote virion assembly via interaction with RNA.
    J Virol. 2000 Apr;74(7):3046-57 PMID: 10708419
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7601664
Published
2007-04-18
Epub
2007-00-29
Pages
2218-26
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1852790
Subset
IM
Grants
NIGMS NIH HHS · P50 GM082545 · United States
NIGMS NIH HHS · P01 GM066521 · United States
NIGMS NIH HHS · F32 GM075543 · United States
NIGMS NIH HHS · P01 GM66521 · United States
PHS HHS · A145405 · United States
External Links
PubMed source DOI: 10.1038/sj.emboj.7601664 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2