%0 Journal Article
%A Batra-Safferling, R.
%A Abarca-Heidemann, K.
%A Körschen, H. G.
%A Tziatzios, C.
%A Stoldt, M.
%A Budyak, I.
%A Willbold, D.
%A Schwalbe, H.
%A Klein-Seetharaman, J.
%A Kaupp, U. B.
%T Glutamic acid-rich proteins of rod photoreceptors are natively unfolded
%J The journal of biological chemistry
%V 281
%@ 0021-9258
%C Bethesda, Md.
%I Soc.
%M PreJuSER-49529
%P 1449 - 1460
%D 2006
%Z Record converted from VDB: 12.11.2012
%X Broadly neutralizing HIV antibodies (bNAbs) can recognize carbohydrate-dependent epitopes on gp120. In contrast to previously characterized glycan-dependent bNAbs that recognize high-mannose N-glycans, PGT121 binds complex-type N-glycans in glycan microarrays. We isolated the B-cell clone encoding PGT121, which segregates into PGT121-like and 10-1074-like groups distinguished by sequence, binding affinity, carbohydrate recognition, and neutralizing activity. Group 10-1074 exhibits remarkable potency and breadth but no detectable binding to protein-free glycans. Crystal structures of unliganded PGT121, 10-1074, and their likely germ-line precursor reveal that differential carbohydrate recognition maps to a cleft between complementarity determining region (CDR)H2 and CDRH3. This cleft was occupied by a complex-type N-glycan in a "liganded" PGT121 structure. Swapping glycan contact residues between PGT121 and 10-1074 confirmed their importance for neutralization. Although PGT121 binds complex-type N-glycans, PGT121 recognized high-mannose-only HIV envelopes in isolation and on virions. As HIV envelopes exhibit varying proportions of high-mannose- and complex-type N-glycans, these results suggest promiscuous carbohydrate interactions, an advantageous adaptation ensuring neutralization of all viruses within a given strain.
%K J (WoSType)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:23115339
%U <Go to ISI:>//WOS:000234652000022
%R 10.1074/jbcM505012200
%U https://juser.fz-juelich.de/record/49529