Multisite and multivalent binding between cyanovirin-N and branched oligomannosides: calorimetric and NMR characterization.
Binding of the protein cyanovirin-N to oligomannose-8 and oligomannose-9 of gp120 is crucially involved in its potent virucidal activity against the human immunodeficiency virus (HIV). The interaction between cyanovirin-N and these oligosaccharides has not been thoroughly characterized due to aggregation of the oligosaccharide-protein complexes. Here, cyanovirin-N's interaction with a nonamannoside, a structural analog of oligomannose-9, has been studied by nuclear magnetic resonance and isothermal titration calorimetry. The nonamannoside interacts with cyanovirin-N in a multivalent fashion, resulting in tight complexes with an average 1:1 stoichiometry. Like the nonamannoside, an alpha1-->2-linked trimannoside substructure interacts with cyanovirin-N at two distinct protein subsites. The chitobiose and internal core trimannoside substructures of oligomannose-9 are not recognized by cyanovirin-N, and binding of the core hexamannoside occurs at only one of the sites on the protein. This is the first detailed analysis of a biologically relevant interaction between cyanovirin-N and high-mannose oligosaccharides of HIV-1 gp120.
Shenoy
Shilpa R
SR
Molecular Targets Discovery Program, NCI Center for Cancer Research, National Cancer Institute, NCI-Frederick, Frederick, MD 21702, USA.
Barrientos
Laura G
LG
Ratner
Daniel M
DM
O'Keefe
Barry R
BR
Seeberger
Peter H
PH
Gronenborn
Angela M
AM
Boyd
Michael R
MR
D001426:Bacterial Proteins; D001665:Binding Sites; D002151:Calorimetry; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D004187:Disaccharides / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D013816:Thermodynamics
D001426:Bacterial Proteins; D002352:Carrier Proteins; D004187:Disaccharides; D009844:Oligosaccharides; C028569:oligomannoside; C107733:cyanovirin N; C032438:chitobiose