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A cis-proline in alpha-hemoglobin stabilizing protein directs the structural reorganization of alpha-hemoglobin

Citation

Gell, DA and Feng, L and Zhou, S and Jeffrey, PD and Bendak, K and Gow, A and Weiss, MJ and Shi, Y and Mackay, JP, A cis-proline in alpha-hemoglobin stabilizing protein directs the structural reorganization of alpha-hemoglobin, Journal of Biological Chemistry, 284, (43) pp. 29462-29469. ISSN 0021-9258 (2009) [Refereed Article]

DOI: doi:10.1074/jbc.M109.027045

Abstract

α-Hemoglobin (αHb) stabilizing protein (AHSP) is expressed in erythropoietic tissues as an accessory factor in hemoglobin synthesis. AHSP forms a specific complex with αHb and suppresses the heme-catalyzed evolution of reactive oxygen species by converting αHb to a conformation in which the heme is coordinated at both axial positions by histidine side chains (bis-histidyl coordination). Currently, the detailed mechanism by which AHSP induces structural changes in αHb has not been determined. Here, we present x-ray crystallography, NMR spectroscopy, and mutagenesis data that identify, for the first time, the importance of an evolutionarily conserved proline, Pro30, in loop 1 of AHSP. Mutation of Pro30 to a variety of residue types results in reduced ability to convert αHb. In complex with-Hb, AHSP Pro30 adopts a cis-peptidyl conformation and makes contact with the N terminus of helix G in αHb. Mutations that stabilize the cis-peptidyl conformation of free AHSP, also enhance the αHb conversion activity. These findings suggest that AHSP loop 1 can transmit structural changes to the heme pocket of αHb, and, more generally, highlight the importance of cis-peptidyl prolyl residues in defining the conformation of regulatory protein loops. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Structural Biology (incl. Macromolecular Modelling)
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Biological Sciences
Author:Gell, DA (Dr David Gell)
ID Code:64524
Year Published:2009
Web of Science® Times Cited:15
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-08-11
Last Modified:2011-07-28
Downloads:0

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