In:
ChemBioChem, Wiley, Vol. 18, No. 8 ( 2017-04-18), p. 764-771
Abstract:
Man 9 GlcNAc 2 (Man‐9) present at the surface of HIV makes up the binding sites of several HIV‐neutralizing agents and the mammalian lectin DC‐SIGN, which is involved in cellular immunity and trans‐infections. We describe the conformational properties of Man‐9 in its free state and when bound by the HIV entry‐inhibitor protein microvirin (MVN), and define the minimum epitopes of both MVN and DC‐SIGN by using NMR spectroscopy. To facilitate the implementation of 3D 13 C‐edited spectra to deconvolute spectral overlap and to determine the solution structure of Man‐9, we developed a robust expression system for the production of 13 C, 15 N‐labeled glycans in mammalian cells. The studies reveal that Man‐9 interacts with HIV‐binding proteins through distinct epitopes and adopts diverse conformations in the bound state. In combination with molecular dynamics simulations we observed receptor‐bound conformations to be sampled by Man‐9 in the free state, thus suggesting a conformational selection mechanism for diverse recognition.
Type of Medium:
Online Resource
ISSN:
1439-4227
,
1439-7633
DOI:
10.1002/cbic.201600665
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
2020469-3
SSG:
12
