title: NMR study into the mechanism of recognition of the degree of polymerization by oligo/polysialic acid antibodies.
abstract: Oligo/polysialic acids consisting of consecutive α(2,8)-linkages on gangliosides and glycoproteins play a role in cell adhesion and differentiation events in a manner that is dependent on the degree of polymerization (DP). Anti-oligo/polysialic acid antibodies often have DP-dependent antigenic specificity, and such unique antibodies are often used in biological studies for the detection and differentiation of oligo/polysialic acids. However, molecular mechanisms remain unclear. We here use NMR techniques to analyze the binding epitopes of the anti-oligo/polysialic acid monoclonal antibodies (mAb) A2B5 and 12E3. The mAb A2B5, which has a preference for trisialic acid, recognizes sialic acid residues at the non-reducing terminus and those in nascent units. On the other hand, mAb 12E3, which prefers oligo/polysialic acids of more than six sugar units, recognizes inner sialic acid residues. In both structural complexes, the interresidue transferred NOE correlations are significantly different from those arising from analogs of the free states, indicating that the bound and free sugar conformations are distinct. The ability of the two mAbs to distinguish the chain lengths comes from different binding epitopes and possibly from the conformational differences in the oligo/polysialic acids. Information on the recognition modes is needed for the structural design of immunoreactive antigens for the development of high-affinity anti-polysialic acid antibodies and of related vaccines against pathogenic, polysialic acid-coated bacteria.
authors: Structural Glycobiology Team, RIKEN ASI, Saitama 351-0198, Japan. shanashima@riken.jp
authors: Shinya
authors: S
authors: Hanashima
authors: Chihiro
authors: C
authors: Sato
authors: Hiroshi
authors: H
authors: Tanaka
authors: Takashi
authors: T
authors: Takahashi
authors: Ken
authors: K
authors: Kitajima
authors: Yoshiki
authors: Y
authors: Yamaguchi
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry; D002240:Carbohydrate Sequence; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D058105:Polymerization; D012794:Sialic Acids / Q000737:chemistry*
chemical_list: D000911:Antibodies, Monoclonal; D012794:Sialic Acids; C021319:polysialic acid
keywords: Antibody; Conformation; Polysialic acid; STD-NMR; TR-NOE