TY  - JOUR
AU  - Batra-Safferling, R.
AU  - Abarca-Heidemann, K.
AU  - Körschen, H. G.
AU  - Tziatzios, C.
AU  - Stoldt, M.
AU  - Budyak, I.
AU  - Willbold, D.
AU  - Schwalbe, H.
AU  - Klein-Seetharaman, J.
AU  - Kaupp, U. B.
TI  - Glutamic acid-rich proteins of rod photoreceptors are natively unfolded
JO  - The journal of biological chemistry
VL  - 281
SN  - 0021-9258
CY  - Bethesda, Md.
PB  - Soc.
M1  - PreJuSER-49529
SP  - 1449 - 1460
PY  - 2006
N1  - Record converted from VDB: 12.11.2012
AB  - 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.
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:23115339
UR  - <Go to ISI:>//WOS:000234652000022
DO  - DOI:10.1074/jbcM505012200
UR  - https://juser.fz-juelich.de/record/49529
ER  -