1cbm: Difference between revisions

Revision as of 12:33, 2 May 2008

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

OverviewOverview

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.

About this StructureAbout this Structure

1CBM is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Fri May 2 12:33:22 2008

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OCA

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 [[Image:1cbm.jpg|left|200px]]
- {{Structure
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+The line below this paragraph, containing "STRUCTURE_1cbm", creates the "Structure Box" on the page.
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-}}
 '''THE 1.8 ANGSTROM STRUCTURE OF CARBONMONOXY-BETA4 HEMOGLOBIN: ANALYSIS OF A HOMOTETRAMER WITH THE R QUATERNARY STRUCTURE OF LIGANDED ALPHA2BETA2 HEMOGLOBIN'''
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 [[Category: Arnone, A.]]
 [[Category: Borgstahl, G E.O.]]
-[[Category: oxygen transport]]
+[[Category: Oxygen transport]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 12:33:22 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:18:34 2008''