1cbm

From Proteopedia

Revision as of 13:35, 15 February 2008

THE 1.8 ANGSTROM STRUCTURE OF CARBONMONOXY-BETA4 HEMOGLOBIN: ANALYSIS OF A HOMOTETRAMER WITH THE R QUATERNARY STRUCTURE OF LIGANDED ALPHA2BETA2 HEMOGLOBIN

Overview

The beta-chains isolated from the human hemoglobin alpha 2 beta 2, heterotetramer self-assemble to form a beta 4 homotetramer. We report the, structure of the carbonmonoxy-beta 4 (CO beta 4) tetramer refined at a, resolution of 1.8 A. Compared to the three known quaternary structures of, human hemoglobin, the T state, the R state and the R2 state, the, quaternary structure of CO beta 4 most closely resembles the R state., While the degree of structural similarity between CO beta 4 and the R, state of liganded alpha 2 beta 2 is quite high, differences between the, alpha and beta-chain sequences result in interesting alternative packing, arrangements at the subunit interfaces of CO beta 4. In particular, Arg40, beta and Asp99 beta interact across the CO beta 4 equivalent of the alpha, 1 beta 2 interface to form two symmetry-related salt bridges that have no, counterpart in either liganded or deoxyhemoglobin. Because these salt, bridges are near a 2-fold symmetry axis, steric constraints prevent their, simultaneous formation, and electron density images of Arg40 beta and, Asp99 beta show equally populated dual conformations for the side-chains, of both residues. Relative to the liganded alpha 2 beta 2 tetramer, the, Arg40 beta...Asp99 beta salt bridges introduce ionic interactions that, should strengthen the CO beta 4 tetramer. The CO beta 4 equivalent of the, alpha 1 alpha 2 and beta 1 beta 2 interfaces strengthens the tetramer, relative to the liganded alpha 2 beta 2 tetramer by tethering both ends of, the central cavity. (The entrance to the central cavity is altered so that, the N termini move closer together and the C termini further apart, forming an anion binding pocket that is absent in liganded alpha 2 beta 2, hemoglobin.) In contrast, analysis of the CO beta 4 counterpart of the, alpha 1 beta 1 interface indicates that this interface is weakened in the, CO beta 4 tetramer. These differences in interface stability provide a, structural explanation for the published observation that the alpha 2 beta, 2 tetramer assembles via a stable alpha 1 beta 1 dimer intermediate, whereas assembly of the CO beta 4 tetramer is characterized more, accurately by a monomer-tetramer equilibrium.

Disease

Known diseases associated with this structure: Erythremias, beta- OMIM:[141900], HPFH, deletion type OMIM:[141900], Heinz body anemias, beta- OMIM:[141900], Methemoglobinemias, beta- OMIM:[141900], Sickle cell anemia OMIM:[141900], Thalassemia-beta, dominant inclusion-body OMIM:[141900], Thalassemias, beta- OMIM:[141900]

About this Structure

1CBM is a Single protein structure of sequence from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.

Reference

The 1.8 A structure of carbonmonoxy-beta 4 hemoglobin. Analysis of a homotetramer with the R quaternary structure of liganded alpha 2 beta 2 hemoglobin., Borgstahl GE, Rogers PH, Arnone A, J Mol Biol. 1994 Feb 25;236(3):817-30. PMID:8114096

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