1CBM

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

1CBM の概要

• エントリーDOI: 10.2210/pdb1cbm/pdb
• 分子名称: HEMOGLOBIN BETA 4 (CARBONMONOXY), SULFATE ION, PROTOPORPHYRIN IX CONTAINING FE, ... (5 entities in total)
• 機能のキーワード: oxygen transport
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 66523.03

構造登録者

Borgstahl, G.E.O.,Arnone, A. (登録日: 1993-02-18, 公開日: 1994-07-31, 最終更新日: 2024-05-22)

主引用文献

Borgstahl, G.E.,Rogers, P.H.,Arnone, A.
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.
J.Mol.Biol., 236:817-830, 1994

PubMed Abstract: 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.

PubMed: 8114096
DOI: 10.1006/jmbi.1994.1191

実験手法

X-RAY DIFFRACTION (1.74 Å)