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PDBsum entry 1cbm
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Oxygen transport
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PDB id
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1cbm
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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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.
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Authors
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G.E.Borgstahl,
P.H.Rogers,
A.Arnone.
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Ref.
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J Mol Biol, 1994,
236,
817-830.
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PubMed id
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Abstract
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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.
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