In:
eLife, eLife Sciences Publications, Ltd, Vol. 7 ( 2018-11-07)
Abstract:
VRC01 broadly neutralizing antibodies (bnAbs) target the CD4-binding site (CD4BS) of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein (Env). Unlike mature antibodies, corresponding VRC01 germline precursors poorly bind to Env. Immunogen design has mostly relied on glycan removal from trimeric Env constructs and has had limited success in eliciting mature VRC01 bnAbs. To better understand elicitation of such bnAbs, we characterized the inferred germline precursor of VRC01 in complex with a modified trimeric 426c Env by cryo-electron microscopy and a 426c gp120 core by X-ray crystallography, biolayer interferometry, immunoprecipitation, and glycoproteomics. Our results show VRC01 germline antibodies interacted with a wild-type 426c core lacking variable loops 1–3 in the presence and absence of a glycan at position Asn276, with the latter form binding with higher affinity than the former. Interactions in the presence of an Asn276 oligosaccharide could be enhanced upon carbohydrate shortening, which should be considered for immunogen design.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.37688.001
DOI:
10.7554/eLife.37688.002
DOI:
10.7554/eLife.37688.003
DOI:
10.7554/eLife.37688.004
DOI:
10.7554/eLife.37688.005
DOI:
10.7554/eLife.37688.006
DOI:
10.7554/eLife.37688.007
DOI:
10.7554/eLife.37688.008
DOI:
10.7554/eLife.37688.009
DOI:
10.7554/eLife.37688.010
DOI:
10.7554/eLife.37688.011
DOI:
10.7554/eLife.37688.012
DOI:
10.7554/eLife.37688.013
DOI:
10.7554/eLife.37688.014
DOI:
10.7554/eLife.37688.015
DOI:
10.7554/eLife.37688.016
DOI:
10.7554/eLife.37688.017
DOI:
10.7554/eLife.37688.018
DOI:
10.7554/eLife.37688.019
DOI:
10.7554/eLife.37688.020
DOI:
10.7554/eLife.37688.021
DOI:
10.7554/eLife.37688.022
DOI:
10.7554/eLife.37688.023
DOI:
10.7554/eLife.37688.041
DOI:
10.7554/eLife.37688.042
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2018
detail.hit.zdb_id:
2687154-3
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