Hyaluronan Recognition Mode of CD44 Revealed by Cross-saturation and Chemical Shift Perturbation Experiments

• Published in: The Journal of biological chemistry Vol. 278; no. 44; pp. 43550 - 43555
• Main Authors: Takeda, Mitsuhiro, Terasawa, Hiroaki, Sakakura, Masayoshi, Yamaguchi, Yoshiki, Kajiwara, Masahiro, Kawashima, Hiroto, Miyasaka, Masayuki, Shimada, Ichio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31.10.2003; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Binding Sites; Humans; Hyaluronan Receptors - chemistry; Hyaluronic Acid - chemistry; Hyaluronic Acid - metabolism; Ligands; Magnetic Resonance Spectroscopy; Models, Biological; Molecular Sequence Data; Oxidation-Reduction; Protein Binding; Protein Conformation; Protein Folding; Protein Structure, Secondary; Protein Structure, Tertiary; Sequence Homology, Amino Acid
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M308199200

CD44 is the main cell surface receptor for hyaluronic acid (HA) and contains a functional HA-binding domain (HABD) composed of a Link module with N- and C-terminal extensions. The contact residues of human CD44 HABD for HA have been determined by cross-saturation experiments and mapped on the topology of CD44 HABD, which we elucidated by NMR. The contact residues are distributed in both the consensus fold for the Link module superfamily and the additional structural elements consisting of the flanking regions. Interestingly, the contact residues exhibit small changes in chemical shift upon HA binding. In contrast, the residues with large chemical shift changes are localized in the C-terminal extension and the first α-helix and are generally inconsistent with the contact residues. These results suggest that, upon ligand binding, the C-terminal extension and the first α-helix undergo significant conformational changes, which may account for the broad ligand specificity of CD44 HABD.