Universität zu Köln

Gristick, Harry B., von Boehmer, Lotta ORCID: 0000-0001-8018-1814, West, Anthony P., Jr., Schamber, Michael, Gazumyan, Anna, Golijanin, Jovana, Seaman, Michael S., Faetkenheuer, Gerd, Klein, Florian, Nussenzweig, Michel C. and Bjorkman, Pamela J. (2016). Natively glycosylated HIV-1 Env structure reveals new mode for antibody recognition of the CD4-binding site. Nat. Struct. Mol. Biol., 23 (10). S. 906 - 916. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1545-9985

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Abstract

HIV-1 vaccine design is informed by structural studies elucidating mechanisms by which broadly neutralizing antibodies (bNAbs) recognize and/or accommodate N-glycans on the trimeric envelope glycoprotein (Env). Variability in high-mannose and complex-type Env glycoforms leads to heterogeneity that usually precludes visualization of the native glycan shield. We present 3.5-angstrom- and 3.9-angstrom-resolution crystal structures of the HIV-1 Env trimer with fully processed and native glycosylation, revealing a glycan shield of high-mannose and complex-type N-glycans, which we used to define complete epitopes of two bNAbs. Env trimer was complexed with 10-1074 (against the V3-loop) and IOMA, a new CD4-binding site (CD4bs) antibody. Although IOMA derives from VH1-2*02, the germline gene of CD4bs-targeting VRC01-class bNAbs, its light chain lacks the short CDRL3 that defines VRC01-class bNAbs. Thus IOMA resembles 8ANC131-class/VH1-46 derived CD4bs bNAbs, which have normal-length CDRL3s. The existence of bNAbs that combine features of VRC01-class and 8ANC131-class antibodies has implications for immunization strategies targeting VRC01-like bNAbs.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gristick, Harry B. UNSPECIFIED UNSPECIFIED UNSPECIFIED von Boehmer, Lotta UNSPECIFIED orcid.org/0000-0001-8018-1814 UNSPECIFIED West, Anthony P., Jr. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schamber, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Gazumyan, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Golijanin, Jovana UNSPECIFIED UNSPECIFIED UNSPECIFIED Seaman, Michael S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Faetkenheuer, Gerd UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Nussenzweig, Michel C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bjorkman, Pamela J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-261735
DOI:	10.1038/nsmb.3291
Journal or Publication Title:	Nat. Struct. Mol. Biol.
Volume:	23
Number:	10
Page Range:	S. 906 - 916
Date:	2016
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	1545-9985
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BROADLY NEUTRALIZING ANTIBODIES; N-GLYCAN RECOGNITION; ENVELOPE GLYCOPROTEIN; MATURATION PATHWAY; CRYSTAL-STRUCTURE; B-CELLS; POTENT; GERMLINE; COMPLEX; 8ANC195 Multiple languages Biochemistry & Molecular Biology; Biophysics; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26173