1jq0
Mutation that destabilize the gp41 core: determinants for stabilizing the SIV/CPmac envelope glycoprotein complex. Mutant structure.
|
OverviewOverview
The human and simian immunodeficiency viruses (HIV and SIV) envelope, glycoprotein consists of a trimer of two noncovalently and weakly, associated subunits, gp120 and gp41. Upon binding of gp120 to cellular, receptors, this labile native envelope complex undergoes conformational, changes, resulting in a stable trimer-of-hairpins structure in gp41., Formation of the hairpin structure is thought to mediate membrane fusion, by placing the viral and cellular membranes in close proximity. An in, vitro-derived variant of SIVmac251, denoted CPmac, has acquired an, unusually stable virion-associated gp120-gp41 complex. This unique, phenotype is conferred by five amino acid substitutions in the gp41, ectodomain. Here we characterize the structural and physicochemical, properties of the N40(L6)C38 model of the CPmac gp41 core. The 1.7-A, resolution crystal structure of N40(L6)C38 is very similar to the, six-helix bundle structure present in the parent SIVmac251 gp41. In both, structures, three N40 peptides form a central three-stranded coiled coil, and three C38 peptides pack in an antiparallel orientation into, hydrophobic grooves on the coiled-coil surface. Thermal unfolding studies, show that the CPmac mutations destabilize the SIVmac251 six-helix bundle, by 15 kJ/mol. Our results suggest that the formation of the gp41, trimer-of-hairpins structure is thermodynamically coupled to the, conformational stability of the native envelope glycoprotein and raise the, intriguing possibility that introduction of mutations to destabilize the, six-helix bundle may lead to the stabilization of the trimeric gp120-gp41, complex. This study suggests a potential strategy for the production of, stably folded envelope protein immunogens for HIV vaccine development.
About this StructureAbout this Structure
1JQ0 is a Single protein structure of sequence from Simian immunodeficiency virus. Full crystallographic information is available from OCA.
ReferenceReference
Mutations that destabilize the gp41 core are determinants for stabilizing the simian immunodeficiency virus-CPmac envelope glycoprotein complex., Liu J, Wang S, Hoxie JA, LaBranche CC, Lu M, J Biol Chem. 2002 Apr 12;277(15):12891-900. Epub 2002 Feb 5. PMID:11830586
Page seeded by OCA on Thu Nov 8 14:13:52 2007