Proteolytic refolding of the HIV-1 capsid protein amino-terminus facilitates viral core assembly. NLM AIDSLINE Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

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Proteolytic refolding of the HIV-1 capsid protein amino-terminus facilitates viral core assembly.

EMBO J. 1998 Mar 16;17(6):1555-68. Unique Identifier : AIDSLINE MED/98169372
von Schwedler UK; Stemmler TL; Klishko VY; Li S; Albertine KH; Davis DR; Sundquist WI; Department of Biochemistry, University of Utah, Salt Lake City, UT; 84132, USA.

Abstract: After budding, the human immunodeficiency virus (HIV) must mature' into an infectious viral particle. Viral maturation requires proteolytic processing of the Gag polyprotein at the matrix-capsid junction, which liberates the capsid (CA) domain to condense from the spherical protein coat of the immature virus into the conical core of the mature virus. We propose that upon proteolysis, the amino-terminal end of the capsid refolds into a beta-hairpin/helix structure that is stabilized by formation of a salt bridge between the processed amino-terminus (Pro1) and a highly conserved aspartate residue (Asp51). The refolded amino-terminus then creates a new CA-CA interface that is essential for assembling the condensed conical core. Consistent with this model, we found that recombinant capsid proteins with as few as four matrix residues fused to their amino-termini formed spheres in vitro, but that removing these residues refolded the capsid amino-terminus and redirected protein assembly from spheres to cylinders. Moreover, point mutations throughout the putative CA-CA interface blocked capsid assembly in vitro, core assembly in vivo and viral infectivity. Disruption of the conserved amino-terminal capsid salt bridge also abolished the infectivity of Moloney murine leukemia viral particles, suggesting that lenti- and oncoviruses mature via analogous pathways.
Keywords: *Capsid/CHEMISTRY *HIV-1/PHYSIOLOGY *Protein Folding *Virus Assembly/PHYSIOLOGY

KWDcapsid/chemistryKWDhiv-1/physiologyKWDproteinfoldingKWDvirusassembly/physiology
980730
M9871325

Copyright © 1998 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

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