TY - JOUR
T1 - Atomic structure of a thermostable subdomain of HIV-1 gp41
AU - Tan, Kemin
AU - Liu, Jin Huan
AU - Wang, Jia Huai
AU - Shen, Steven
AU - Lu, Min
PY - 1997/11/11
Y1 - 1997/11/11
N2 - Infection by HIV-I involves the fusion of viral and cellular membranes with subsequent transfer of viral genetic material into the cell. The HIV-1 envelope glycoprotein that mediates fusion consists of the surface subunit gp120 and the transmembrane subunit gp41.gp120 directs virion attachment to the cell-surface receptors. and gp41 then promotes vital-cell membrane fusion. A soluble, α-helical, trimeric complex within gp41 composed of N- terminal and C-terminal extraviral segments has been proposed to represent the core of the fusion-active conformation of the HIV-1 envelope. A thermostable subdomain denoted N34(L6)C28 can be formed by the N-34 and C-28 peptides connected by a flexible linker in place of the disulfide-bonded loop region. Three-dimensional structure of N34(L6)C28 reveals that three molecules fold into a six-stranded helical bundle. Three N-terminal helices within the bundle form a central, parallel, trimeric coiled coil, whereas three C-terminal helices pack in the reverse direction into three hydrophobic grooves on the surface of the N-terminal trimer. This thermostable subdomain displays the salient features of the core structure of the isolated gp41 subunit and thus provides a possible target for therapeutics designed selectively to block HIV-1 entry.
AB - Infection by HIV-I involves the fusion of viral and cellular membranes with subsequent transfer of viral genetic material into the cell. The HIV-1 envelope glycoprotein that mediates fusion consists of the surface subunit gp120 and the transmembrane subunit gp41.gp120 directs virion attachment to the cell-surface receptors. and gp41 then promotes vital-cell membrane fusion. A soluble, α-helical, trimeric complex within gp41 composed of N- terminal and C-terminal extraviral segments has been proposed to represent the core of the fusion-active conformation of the HIV-1 envelope. A thermostable subdomain denoted N34(L6)C28 can be formed by the N-34 and C-28 peptides connected by a flexible linker in place of the disulfide-bonded loop region. Three-dimensional structure of N34(L6)C28 reveals that three molecules fold into a six-stranded helical bundle. Three N-terminal helices within the bundle form a central, parallel, trimeric coiled coil, whereas three C-terminal helices pack in the reverse direction into three hydrophobic grooves on the surface of the N-terminal trimer. This thermostable subdomain displays the salient features of the core structure of the isolated gp41 subunit and thus provides a possible target for therapeutics designed selectively to block HIV-1 entry.
UR - http://www.scopus.com/inward/record.url?scp=0030780614&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030780614&partnerID=8YFLogxK
U2 - 10.1073/pnas.94.23.12303
DO - 10.1073/pnas.94.23.12303
M3 - Article
C2 - 9356444
AN - SCOPUS:0030780614
SN - 0027-8424
VL - 94
SP - 12303
EP - 12308
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 23
ER -