1POZ

SOLUTION STRUCTURE OF THE HYALURONAN BINDING DOMAIN OF HUMAN CD44

Summary for 1POZ

• Entry DOI: 10.2210/pdb1poz/pdb
• Related: 1o7b 1o7c
• NMR Information: BMRB: 6093
• Descriptor: CD44 antigen (1 entity in total)
• Functional Keywords: hyaluronan-binding domain, carbohydrate-binding domain, link module, cell adhesion, glycoprotein
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: Q16208
• Total number of polymer chains: 1
• Total formula weight: 17601.49

Authors

Teriete, P.,Banerji, S.,Blundell, C.D.,Kahmann, J.D.,Pickford, A.R.,Wright, A.J.,Campbell, I.D.,Jackson, D.G.,Day, A.J. (deposition date: 2003-06-16, release date: 2004-03-16, Last modification date: 2024-10-30)

Primary citation

Teriete, P.,Banerji, S.,Noble, M.,Blundell, C.D.,Wright, A.J.,Pickford, A.R.,Lowe, E.,Mahoney, D.J.,Tammi, M.I.,Kahmann, J.D.,Campbell, I.D.,Day, A.J.,Jackson, D.G.
Structure of the Regulatory Hyaluronan Binding Domain in the Inflammatory Leukocyte Homing Receptor CD44.
Mol.Cell, 13:483-496, 2004

PubMed Abstract: Adhesive interactions involving CD44, the cell surface receptor for hyaluronan, underlie fundamental processes such as inflammatory leukocyte homing and tumor metastasis. Regulation of such events is critical and appears to be effected by changes in CD44 N-glycosylation that switch the receptor "on" or "off" under appropriate circumstances. How altered glycosylation influences binding of hyaluronan to the lectin-like Link module in CD44 is unclear, although evidence suggests additional flanking sequences peculiar to CD44 may be involved. Here we show using X-ray crystallography and NMR spectroscopy that these sequences form a lobular extension to the Link module, creating an enlarged HA binding domain and a formerly unidentified protein fold. Moreover, the disposition of key N-glycosylation sites reveals how specific sugar chains could alter both the affinity and avidity of CD44 HA binding. Our results provide the necessary structural framework for understanding the diverse functions of CD44 and developing novel therapeutic strategies.

PubMed: 14992719
DOI: 10.1016/S1097-2765(04)00080-2

Experimental method

SOLUTION NMR