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:
CreatorsEmailORCIDORCID Put Code
Gristick, Harry B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Boehmer, LottaUNSPECIFIEDorcid.org/0000-0001-8018-1814UNSPECIFIED
West, Anthony P., Jr.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schamber, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gazumyan, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Golijanin, JovanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seaman, Michael S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Faetkenheuer, GerdUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nussenzweig, Michel C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bjorkman, Pamela J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
BROADLY NEUTRALIZING ANTIBODIES; N-GLYCAN RECOGNITION; ENVELOPE GLYCOPROTEIN; MATURATION PATHWAY; CRYSTAL-STRUCTURE; B-CELLS; POTENT; GERMLINE; COMPLEX; 8ANC195Multiple languages
Biochemistry & Molecular Biology; Biophysics; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/26173

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