1uuh

From Proteopedia

Revision as of 15:03, 15 February 2008

HYALURONAN BINDING DOMAIN OF HUMAN CD44

Overview

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.

Disease

Known diseases associated with this structure: Blood group, Indian system OMIM:[107269], Fertile eunuch syndrome OMIM:[138850], Hypogonadotropic hypogonadism OMIM:[138850]

About this Structure

1UUH is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of the regulatory hyaluronan binding domain in the inflammatory leukocyte homing receptor CD44., Teriete P, Banerji S, Noble M, Blundell CD, Wright AJ, Pickford AR, Lowe E, Mahoney DJ, Tammi MI, Kahmann JD, Campbell ID, Day AJ, Jackson DG, Mol Cell. 2004 Feb 27;13(4):483-96. PMID:14992719

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