In:
The FEBS Journal, Wiley, Vol. 281, No. 13 ( 2014-07), p. 3019-3031
Abstract:
The envelope spike of HIV ‐1, which consists of three external gp120 and three transmembrane gp41 glycoproteins, recognizes its target cells by successively binding to its primary CD 4 receptor and a coreceptor molecule. Until recently, atomic‐resolution structures were available primarily for monomeric HIV ‐1 gp120, in which the V1, V2 and V3 variable loops were omitted (gp120 core ), in complex with soluble CD4 (s CD 4). Differences between the structure of HIV gp120 core in complex with s CD 4 and the structure of unliganded simian immunodeficiency virus gp120 core led to the hypothesis that gp120 undergoes a major conformational change upon s CD 4 binding. To investigate the conformational flexibility of gp120, we generated two forms of mutated gp120 amenable for NMR studies: one with V1, V2 and V3 omitted ( mut gp120 core ) and the other containing the V3 region [ mut gp120 core (+V3)]. The TROSY‐ 1 H‐ 15 N‐HSQC spectra of [ 2 H, 13 C, 15 N]Arg‐labeled and [ 2 H, 13 C, 15 N]Ile‐labeled unliganded mut gp120 core showed many fewer crosspeaks than the expected number, and also many fewer crosspeaks in comparison with the labeled mut gp120 core bound to the CD4‐mimic peptide, CD 4M33. This finding suggests that in the unliganded form, mut gp120 core shows considerable flexibility and motions on the millisecond time scale. In contrast, most of the expected crosspeaks were observed for the unliganded mut gp120 core (+V3), and only a few changes in chemical shift were observed upon CD 4M33 binding. These results indicate that mut gp120 core (+V3) does not show any significant conformational flexibility in its unliganded form and does not undergo any significant conformational change upon CD4M33 binding, underlining the importance of V3 in stabilizing the gp120 core conformation.
Type of Medium:
Online Resource
ISSN:
1742-464X
,
1742-4658
DOI:
10.1111/febs.2014.281.issue-13
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2172518-4
SSG:
12
