2ceo

From Proteopedia

Revision as of 17:09, 18 December 2007

THYROXINE-BINDING GLOBULIN COMPLEX WITH THYROXINE

Overview

The hormones that most directly control tissue activities in health and, disease are delivered by two noninhibitory members of the serpin family of, protease inhibitors, thyroxine-binding globulin (TBG) and, corticosteroid-binding globulin. The structure of TBG bound to tetra-iodo, thyroxine, solved here at 2.8 A, shows how the thyroxine is carried in a, surface pocket on the molecule. This unexpected binding site is confirmed, by mutations associated with a loss of hormone binding in both TBG and, also homologously in corticosteroid-binding globulin. TBG strikingly, differs from other serpins in having the upper half of its main beta-sheet, fully opened, so its reactive center peptide loop can readily move in and, out of the sheet to give an equilibrated binding and release of thyroxine., The entry of the loop triggers a conformational change, with a linked, contraction of the binding pocket and release of the bound thyroxine. The, ready reversibility of this change is due to the unique presence in the, reactive loop of TBG of a proline that impedes the full and irreversible, entry of the loop that occurs in other serpins. Thus, TBG has adapted the, serpin inhibitory mechanism to give a reversible flip-flop transition, from a high-affinity to a low-affinity form. The complexity and ready, triggering of this conformational mechanism strongly indicates that TBG, has evolved to allow a modulated and targeted delivery of thyroxine to the, tissues.

Disease

Known disease associated with this structure: Thyroxine-binding globulin deficiency OMIM:[314200]

About this Structure

2CEO is a Single protein structure of sequence from Homo sapiens with T44 and GOL as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Structural mechanism for the carriage and release of thyroxine in the blood., Zhou A, Wei Z, Read RJ, Carrell RW, Proc Natl Acad Sci U S A. 2006 Sep 5;103(36):13321-6. Epub 2006 Aug 28. PMID:16938877

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