Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

High-resolution structure of a retroviral capsid hexameric amino-terminal domain

An Erratum to this article was published on 21 October 2004


Retroviruses are the aetiological agents of a range of human diseases including AIDS and T-cell leukaemias. They follow complex life cycles, which are still only partly understood at the molecular level. Maturation of newly formed retroviral particles is an essential step in production of infectious virions, and requires proteolytic cleavage of Gag polyproteins in the immature particle to form the matrix, capsid and nucleocapsid proteins present in the mature virion1. Capsid proteins associate to form a dense viral core2 that may be spherical, cylindrical or conical depending on the genus of the virus3. Nonetheless, these assemblies all appear to be composed of a lattice formed from hexagonal rings, each containing six capsid monomers2,4,5. Here, we describe the X-ray structure of an individual hexagonal assembly from N-tropic murine leukaemia virus (N-MLV). The interface between capsid monomers is generally polar, consistent with weak interactions within the hexamer. Similar architectures are probably crucial for the regulation of capsid assembly and disassembly in all retroviruses. Together, these observations provide new insights into retroviral uncoating and how cellular restriction factors may interfere with viral replication.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: The structure of the NTD of N-MLV capsid.
Figure 2: The structure of N-MLV NTD hexameric assembly.
Figure 3: Details of the molecular interactions between monomers at the interface.
Figure 4: Interactions mediated by residues located on or around the β1–β2 hairpin.


  1. 1

    Swanstrom, R. & Wills, J. W. in Synthesis, Assembly and Processing of Viral Proteins (eds Coffin, J. M., Hughes, S. H. & Varmus, H. E.) (Cold Spring Harbor Laboratory Press, New York, 1997)

    Google Scholar 

  2. 2

    Briggs, J. A., Wilk, T., Welker, R., Krausslich, H. G. & Fuller, S. D. Structural organization of authentic, mature HIV-1 virions and cores. EMBO J. 22, 1707–1715 (2003)

    CAS  Article  Google Scholar 

  3. 3

    Nermut, M. V. & Hockley, D. J. Comparative morphology and structural classification of retroviruses. Curr. Top. Microbiol. Immunol. 214, 1–24 (1996)

    CAS  PubMed  Google Scholar 

  4. 4

    Li, S., Hill, C. P., Sundquist, W. I. & Finch, J. T. Image reconstructions of helical assemblies of the HIV-1 CA protein. Nature 407, 409–413 (2000)

    ADS  CAS  Article  Google Scholar 

  5. 5

    Ganser, B. K., Cheng, A., Sundquist, W. I. & Yeager, M. Three-dimensional structure of the M-MuLV CA protein on a lipid monolayer: a general model for retroviral capsid assembly. EMBO J. 22, 2886–2892 (2003)

    CAS  Article  Google Scholar 

  6. 6

    Kingston, R. L. et al. Structure and self-association of the Rous sarcoma virus capsid protein. Struct. Fold. Des. 8, 617–628 (2000)

    CAS  Article  Google Scholar 

  7. 7

    Cornilescu, C. C., Bouamr, F., Yao, X., Carter, C. & Tjandra, N. Structural analysis of the N-terminal domain of the human T-cell leukemia virus capsid protein. J. Mol. Biol. 306, 783–797 (2001)

    CAS  Article  Google Scholar 

  8. 8

    Gamble, T. R. et al. Crystal structure of human cyclophilin A bound to the amino-terminal domain of HIV-1 capsid. Cell 87, 1285–1294 (1996)

    CAS  Article  Google Scholar 

  9. 9

    Gitti, R. K. et al. Structure of the amino-terminal core domain of the HIV-1 capsid protein. Science 273, 231–235 (1996)

    ADS  CAS  Article  Google Scholar 

  10. 10

    Jin, Z., Jin, L., Peterson, D. L. & Lawson, C. L. Model for lentivirus capsid core assembly based on crystal dimers of EIAV p26. J. Mol. Biol. 286, 83–93 (1999)

    CAS  Article  Google Scholar 

  11. 11

    Khorasanizadeh, S., Campos-Olivas, R. & Summers, M. F. Solution structure of the capsid protein from the human T-cell leukemia virus type-I. J. Mol. Biol. 291, 491–505 (1999)

    CAS  Article  Google Scholar 

  12. 12

    Nandhagopal, N. et al. Dimeric Rous sarcoma virus capsid protein structure relevant to immature Gag assembly. J. Mol. Biol. 335, 275–282 (2004)

    CAS  Article  Google Scholar 

  13. 13

    Tang, C., Ndassa, Y. & Summers, M. F. Structure of the N-terminal 283-residue fragment of the immature HIV-1 Gag polyprotein. Nature Struct. Biol. 9, 537–543 (2002)

    CAS  PubMed  Google Scholar 

  14. 14

    Gross, I., Hohenberg, H., Huckhagel, C. & Krausslich, H. G. N-Terminal extension of human immunodeficiency virus capsid protein converts the in vitro assembly phenotype from tubular to spherical particles. J. Virol. 72, 4798–4810 (1998)

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 15

    von Schwedler, U. K. et al. Proteolytic refolding of the HIV-1 capsid protein amino-terminus facilitates viral core assembly. EMBO J. 17, 1555–1568 (1998); corrigendum 19, 2391 (2000)

    CAS  Article  Google Scholar 

  16. 16

    Briggs, J. A. et al. The stoichiometry of Gag protein in HIV-1. Nature Struct. Mol. Biol. 11, 672–675 (2004)

    CAS  Article  Google Scholar 

  17. 17

    Lanman, J. et al. Identification of novel interactions in HIV-1 capsid protein assembly by high-resolution mass spectrometry. J. Mol. Biol. 325, 759–772 (2003)

    CAS  Article  Google Scholar 

  18. 18

    Lanman, J. et al. Key interactions in HIV-1 maturation identified by hydrogen-deuterium exchange. Nature Struct. Mol. Biol. 11, 676–677 (2004)

    CAS  Article  Google Scholar 

  19. 19

    von Schwedler, U. K., Stray, K. M., Garrus, J. E. & Sundquist, W. I. Functional surfaces of the human immunodeficiency virus type 1 capsid protein. J. Virol. 77, 5439–5450 (2003)

    CAS  Article  Google Scholar 

  20. 20

    Forshey, B. M., von Schwedler, U., Sundquist, W. I. & Aiken, C. Formation of a human immunodeficiency virus type 1 core of optimal stability is crucial for viral replication. J. Virol. 76, 5667–5677 (2002)

    CAS  Article  Google Scholar 

  21. 21

    Ganser-Pornillos, B. K., von Schwedler, U. K., Stray, K. M., Aiken, C. & Sundquist, W. I. Assembly properties of the human immunodeficiency virus type 1 CA protein. J. Virol. 78, 2545–2552 (2004)

    CAS  Article  Google Scholar 

  22. 22

    Fassati, A. & Goff, S. P. Characterization of intracellular reverse transcription complexes of Moloney murine leukemia virus. J. Virol. 73, 8919–8925 (1999)

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23

    Fassati, A. & Goff, S. P. Characterization of intracellular reverse transcription complexes of human immunodeficiency virus type 1. J. Virol. 75, 3626–3635 (2001)

    CAS  Article  Google Scholar 

  24. 24

    Karageorgos, L., Li, P. & Burrell, C. Characterization of HIV replication complexes early after cell-to-cell infection. AIDS Res. Hum. Retroviruses 9, 817–823 (1993)

    CAS  Article  Google Scholar 

  25. 25

    Best, S., Le Tissier, P., Towers, G. & Stoye, J. P. Positional cloning of the mouse retrovirus restriction gene Fv1. Nature 382, 826–829 (1996)

    ADS  CAS  Article  Google Scholar 

  26. 26

    Boone, L. R. et al. Reversal of Fv-1 host range by in vitro restriction endonuclease fragment exchange between molecular clones of N-tropic and B-tropic murine leukemia virus genomes. J. Virol. 48, 110–119 (1983)

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27

    Stremlau, M. et al. The cytoplasmic body component TRIM5α restricts HIV-1 infection in Old World monkeys. Nature 427, 848–853 (2004)

    ADS  CAS  Article  Google Scholar 

  28. 28

    Terwilliger, T. C. & Berendzen, J. Automated MAD and MIR structure solution. Acta Crystallogr. D 55, 849–861 (1999)

    CAS  Article  Google Scholar 

  29. 29

    Cowtan, K. ‘dm’: an automated procedure for phase improvement by density modification. Joint CCP4 ESF-EACBM Newsl. Prot. Crystallogr. 31, 34–38 (1994)

    Google Scholar 

  30. 30

    Morris, R. J., Perrakis, A. & Lamzin, V. S. ARP/wARP and automatic interpretation of protein electron density maps. Methods Enzymol. 374, 229–244 (2003)

    CAS  Article  Google Scholar 

Download references


We thank S. Gamblin for assistance in crystal handling.

Author information



Corresponding author

Correspondence to Ian A. Taylor.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Mortuza, G., Haire, L., Stevens, A. et al. High-resolution structure of a retroviral capsid hexameric amino-terminal domain. Nature 431, 481–485 (2004).

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing