Progress in FY2016 was in the following areas: (1) HIV-1 CAPSID ASSEMBLIES: We have obtained quantitative structural constraints for the dimer interface in tubular CA assemblies, using a variety of solid state NMR techniques (BroBaRR, REDOR, NCCN tensor correlation, etc.) Previous studies by crystallography, cryoEM, and solution NMR have resulted in disparate structural models for this critical region of intermolecular association. From our solid state NMR constraints, we have developed a detailed structural model for the dimer interface in the tubular assemblies. This represents the first demonstration that solid state NMR measurements can provide new atomic-level structural information to complement information from cryoEM and crystallography. A paper describing this work has been published recently in JACS. (2) VIRUS-LIKE PARTICLES: We have examined virus-like particles (VLPs) formed by an HIV-1 Gag polyprotein construct that includes part of the MA domain, all of the CA and NC domains, and the SP1 spacer peptide between CA and NC. The VLPs mimic the Gag lattice of immature HIV-1 virions. Solid state NMR data provide strong evidence for alpha-helix formation by a 26-residue segment that spans the CA-SP1 junction. Helix formation by this segment had been proposed to stabilize the immature lattice, making CA-SP1 cleavage a prerequisite for HIV-1 maturation. This work has been published recently in JACS.
