STRUCTURE-FUNCTION STUDIES OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1MATRIX PROTEIN, P17

The human immunodeficiency virus type 1 (HIV-1) matrix protein, p17, p lays important roles in both the early and late stages of the viral li fe cycle, Using our previously determined solution structure of p17, w e have undertaken a rational mutagenesis program aimed at mapping stru cture-function relationships within the molecule.;imino acids hypothes ized to be important for p17 function were mutated and examined for ef fect in an infectious proviral clone of HIV-1. In parallel, we analyze d by nuclear magnetic resonance spectroscopy the structure of recombin ant p17 protein containing such substitutions, These analyses identifi ed three classes of mutants that were defective in viral replication: (i) proteins containing substitutions at internal residues that grossl y distorted the structure of recombinant p17 and prevented viral parti cle formation, (ii) mutations at putative p17 trimer interfaces that a llowed correct folding of recombinant protein but produced virus that was defective in particle assembly, and (iii) substitution of basic re sidues in helix A that caused some relocation of virus assembly to int racellular locations and produced normally budded virions that were co mpletely noninfectious.