Hyaluronan recognition mode of CD44 revealed by cross-saturation and chemical shift perturbation experiments.
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 alpha-helix and are generally inconsistent with the contact residues. These results suggest that, upon ligand binding, the C-terminal extension and the first alpha-helix undergo significant conformational changes, which may account for the broad ligand specificity of CD44 HABD.
Takeda
Mitsuhiro
M
Graduate School of Pharmaceutical Sciences, the University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Terasawa
Hiroaki
H
Sakakura
Masayoshi
M
Yamaguchi
Yoshiki
Y
Kajiwara
Masahiro
M
Kawashima
Hiroto
H
Miyasaka
Masayuki
M
Shimada
Ichio
I
D000595:Amino Acid Sequence; D001665:Binding Sites; D006801:Humans; D018960:Hyaluronan Receptors / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D018960:Hyaluronan Receptors; D008024:Ligands; D006820:Hyaluronic Acid