3WBD

Crystal structure of anti-polysialic acid antibody single chain Fv fragment (mAb735) complexed with octasialic acid

Summary for 3WBD

• Entry DOI: 10.2210/pdb3wbd/pdb
• Related: 1PLG
• Descriptor: single chain Fv fragment of mAb735, N-acetyl-alpha-neuraminic acid-(2-8)-N-acetyl-alpha-neuraminic acid-(2-8)-N-acetyl-alpha-neuraminic acid-(2-8)-N-acetyl-alpha-neuraminic acid-(2-8)-N-acetyl-alpha-neuraminic acid-(2-8)-N-acetyl-alpha-neuraminic acid-(2-8)-N-acetyl-alpha-neuraminic acid, CITRATE ANION, ... (4 entities in total)
• Functional Keywords: beta-sandwich, immunoglobulin fold, single chain fv fragment, anti-polysialic acid, alpha2-8 linked polysialic acid, immune system
• Biological source: Mus musculus (mouse)
• Total number of polymer chains: 2
• Total formula weight: 54780.19

Authors

Nagae, M.,Ikeda, A.,Hanashima, S.,Kitajima, K.,Sato, C.,Yamaguchi, Y. (deposition date: 2013-05-14, release date: 2013-10-16, Last modification date: 2023-11-08)

Primary citation

Nagae, M.,Ikeda, A.,Hane, M.,Hanashima, S.,Kitajima, K.,Sato, C.,Yamaguchi, Y.
Crystal structure of anti-polysialic acid antibody single chain Fv fragment complexed with octasialic acid: insight into the binding preference for polysialic acid.
J.Biol.Chem., 288:33784-33796, 2013

PubMed Abstract: Polysialic acid is a linear homopolymer of α2-8-linked sialic acids attached mainly onto glycoproteins. Cell surface polysialic acid plays roles in cell adhesion and differentiation events in a manner that is often dependent on the degree of polymerization (DP). Anti-oligo/polysialic acid antibodies have DP-dependent antigenic specificity, and such antibodies are widely utilized in biological studies for detecting and distinguishing between different oligo/polysialic acids. A murine monoclonal antibody mAb735 has a unique preference for longer polymers of polysialic acid (DP >10), yet the mechanism of recognition at the atomic level remains unclear. Here, we report the crystal structure of mAb735 single chain variable fragment (scFv735) in complex with octasialic acid at 1.8 Å resolution. In the asymmetric unit, two scFv735 molecules associate with one octasialic acid. In both complexes of the unit, all the complementarity-determining regions except for L3 interact with three consecutive sialic acid residues out of the eight. A striking feature of the complex is that 11 ordered water molecules bridge the gap between antibody and ligand, whereas the direct antibody-ligand interaction is less extensive. The dihedral angles of the trisialic acid unit directly interacting with scFv735 are not uniform, indicating that mAb735 does not strictly favor the previously proposed helical conformation. Importantly, both reducing and nonreducing ends of the bound ligand are completely exposed to solvent. We suggest that mAb735 gains its apparent high affinity for a longer polysialic acid chain by recognizing every three sialic acid units in a paired manner.

PubMed: 24100042
DOI: 10.1074/jbc.M113.496224

Experimental method

X-RAY DIFFRACTION (1.8 Å)