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Structure of the N-terminal 283-residue fragment of the immature HIV-1 Gag polyprotein

Nature Structural Biology volume 9, pages 537–543 (2002)Cite this article

Abstract

The capsid protein (CA) of the mature human immunodeficiency virus (HIV) contains an N-terminal β-hairpin that is essential for formation of the capsid core particle. CA is generated by proteolytic cleavage of the Gag precursor polyprotein during viral maturation. We have determined the NMR structure of a 283-residue N-terminal fragment of immature HIV-1 Gag (Gag283), which includes the intact matrix (MA) and N-terminal capsid (CAN) domains. The β-hairpin is unfolded in Gag283, consistent with the proposal that hairpin formation occurs subsequent to proteolytic cleavage of Gag, triggering capsid assembly. Comparison of the immature and mature CAN structures reveals that β-hairpin formation induces a ∼2 Å displacement of helix 6 and a concomitant displacement of the cyclophylin-A (CypA)-binding loop, suggesting a possible allosteric mechanism for CypA-mediated destabilization of the capsid particle during infectivity.

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Figure 1: Representative NMR spectra obtained for Gag283 and comparisons with the mature CAN domain.
Figure 2: NMR relaxation and chemical shift data that identify regions of structure and mobility.
Figure 3: Stereo views of the MA (residues Gly 2–Tyr 132, top) and CAN (residues Pro 133–Leu 283) domains of the ensemble of 20 final structures of Gag283.
Figure 4: Hydrodynamic properties of Gag283.
Figure 5: Structural changes associated with β-hairpin formation.

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Acknowledgements

Support from the NIAID-NIH is gratefully acknowledged. We thank D. King (U.C. Berkeley) for mass spectral measurements and R. Edwards (HHMI, UMBC) for technical assistance. Y.N. is a Meyerhoff undergraduate scholar.

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  1. Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, 21250, Maryland, USA

    Chun Tang, Yasmine Ndassa & Michael F. Summers

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Correspondence to Michael F. Summers.

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Tang, C., Ndassa, Y. & Summers, M. Structure of the N-terminal 283-residue fragment of the immature HIV-1 Gag polyprotein. Nat Struct Mol Biol 9, 537–543 (2002). https://doi.org/10.1038/nsb806

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