Hepcidin Revisited, Disulfide Connectivity, Dynamics, and Structure

被引：178

作者：

Jordan, John B. ^{[1
]}

Poppe, Leszek ^{[1
]}

Haniu, Mitsuru ^{[2
]}

Arvedson, Tara ^{[3
]}

Syed, Rashid ^{[1
]}

Li, Vivian ^{[1
]}

Kohno, Hiko ^{[2
]}

Kim, Helen ^{[2
]}

Schnier, Paul D. ^{[1
]}

Harvey, Timothy S. ^{[1
]}

Miranda, Les P. ^{[1
]}

Cheetham, Janet ^{[1
]}

Sasu, Barbra J. ^{[3
]}

机构：

[1] Amgen Inc, Dept Mol Struct, Thousand Oaks, CA 91320 USA

[2] Amgen Inc, Dept Prot Sci, Thousand Oaks, CA 91320 USA

[3] Amgen Inc, Dept Hematol, Thousand Oaks, CA 91320 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2009年 / 284卷 / 36期

基金：

美国能源部;

关键词：

AUTOSOMAL-DOMINANT HEMOCHROMATOSIS; ANTIMICROBIAL PEPTIDE HEPCIDIN; CORRELATION NMR-SPECTROSCOPY; BETA-TURN FORMATION; HEREDITARY HEMOCHROMATOSIS; IRON OVERLOAD; COUPLING-CONSTANTS; FERROPORTIN; PROTEINS; EXPRESSION;

D O I：

10.1074/jbc.M109.017764

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：24155 / 24167

页数：13

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