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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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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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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DOI: https://doi.org/10.1038/nsb806
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