Hepcidin Revisited, Disulfide Connectivity, Dynamics, and Structure

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2009 Jun 26

PMID 19553669

Citations 63

Authors

John B Jordan

Leszek Poppe

Mitsuru Haniu

Tara Arvedson

Rashid Syed

Vivian Li

Hiko Kohno

Helen Kim

Paul D Schnier

Timothy S Harvey

Les P Miranda

Janet Cheetham

Barbra J Sasu

Affiliations

Soon will be listed here.

Abstract

Hepcidin is a tightly folded 25-residue peptide hormone containing four disulfide bonds, which has been shown to act as the principal regulator of iron homeostasis in vertebrates. We used multiple techniques to demonstrate a disulfide bonding pattern for hepcidin different from that previously published. All techniques confirmed the following disulfide bond connectivity: Cys(1)-Cys(8), Cys(3)-Cys(6), Cys(2)-Cys(4), and Cys(5)-Cys(7). NMR studies reveal a new model for hepcidin that, at ambient temperatures, interconverts between two different conformations, which could be individually resolved by temperature variation. Using these methods, the solution structure of hepcidin was determined at 325 and 253 K in supercooled water. X-ray analysis of a co-crystal with Fab appeared to stabilize a hepcidin conformation similar to the high temperature NMR structure.

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