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2i83

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2i83

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hyaluronan-binding domain of CD44 in its ligand-bound form

Contents

Overview

CD44, a major cell surface receptor for hyaluronan (HA), contains a, functional domain responsible for HA binding at its N terminus (residues, 21-178). Accumulating evidence indicates that proteolytic cleavage of CD44, in its extracellular region (residues 21-268) leads to enhanced tumor cell, migration and invasion. Hence, understanding the mechanisms underlying the, CD44 proteolytic cleavage is important for understanding the mechanism of, CD44-mediated tumor progression. Here we present the NMR structure of the, HA-binding domain of CD44 in its HA-bound state. The structure is composed, of the Link module (residues 32-124) and an extended lobe (residues 21-31, and 125-152). Interestingly, a comparison of its unbound and HA-bound, structures revealed that rearrangement of the beta-strands in the extended, lobe (residues 143-148) and disorder of the structure in the following, C-terminal region (residues 153-169) occurred upon HA binding, which is, consistent with the results of trypsin proteolysis studies of the CD44, HA-binding domain. The order-to-disorder transition of the C-terminal, region by HA binding may be involved in the CD44-mediated cell migration.

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

2I83 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Ligand-induced structural changes of the CD44 hyaluronan-binding domain revealed by NMR., Takeda M, Ogino S, Umemoto R, Sakakura M, Kajiwara M, Sugahara KN, Hayasaka H, Miyasaka M, Terasawa H, Shimada I, J Biol Chem. 2006 Dec 29;281(52):40089-95. Epub 2006 Nov 2. PMID:17085435

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