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Conformational rearrangements required of the V 3 loop of HIV‐1 gp120 for proteolytic cleavage and infection
Author(s) -
Johnson Michael E.,
Lin Zhaolan,
Padmanabhan Kaillathe,
Tulinsky Alexander,
Kahn Michael
Publication year - 1994
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)80618-7
Subject(s) - cleavage (geology) , proteases , thrombin , stereochemistry , serine protease , chemistry , serine , protease , trypsin , human immunodeficiency virus (hiv) , binding site , hiv 1 protease , peptide , biochemistry , enzyme , biology , virology , paleontology , platelet , fracture (geology) , immunology
HIV gp120 is specifically cleaved at a single site in the V 3 loop between Arg 315 and Ala 316 by thrombin. Previous observations by others have indicated that binding to CD4 enhances the rate of V 3 loop cleavage, and that this cleavage is a prerequisite for HIV infection. Other observations also suggest that the cleavage site is in a type II β‐turn centered at Pro 313 ‐Gly 314 . However, our docking experiments indicate that this conformation cannot dock to thrombin and other trypsin‐like serine proteases. Thus, based on the thrombin‐bound conformation of peptide substrates, we propose that CD4 binding, at a site remote from the V 3 loop, induces and stabilizes a trans to cis isomerization of the highly conserved residue Pro 313 , and that this conformational shift is a prerequisite for cleavage by a ‘thrombin‐like’ cellular pro tease and subsequent infection.