1JQ0

Mutation that destabilize the gp41 core: determinants for stabilizing the SIV/CPmac envelope glycoprotein complex. Mutant structure.

1JQ0 の概要

• エントリーDOI: 10.2210/pdb1jq0/pdb
• 関連するPDBエントリー: 1JPX 1QBZ
• 分子名称: gp41 envelope protein (2 entities in total)
• 機能のキーワード: gp41, siv, hiv-1, membrane fusion, six-helix bundle, trimer-of-hairpins, viral protein
• 由来する生物種: Simian immunodeficiency virus; 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9835.16

構造登録者

Liu, J.,Wang, S.,LaBranche, C.C.,Hoxie, J.A.,Lu, M. (登録日: 2001-08-03, 公開日: 2002-04-24, 最終更新日: 2023-08-16)

主引用文献

Liu, J.,Wang, S.,Hoxie, J.A.,LaBranche, C.C.,Lu, M.
Mutations that destabilize the gp41 core are determinants for stabilizing the simian immunodeficiency virus-CPmac envelope glycoprotein complex.
J.Biol.Chem., 277:12891-12900, 2002

PubMed Abstract: 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.

PubMed: 11830586
DOI: 10.1074/jbc.M110315200

実験手法

X-RAY DIFFRACTION (1.7 Å)