3IA3

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

3IA3 の概要

• エントリーDOI: 10.2210/pdb3ia3/pdb
• 分子名称: Alpha-hemoglobin-stabilizing protein, Hemoglobin subunit alpha, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total)
• 機能のキーワード: hemoglobin, cis-proline, ahsp, stabilization, chaperone, cytoplasm, polymorphism, acetylation, disease mutation, glycation, glycoprotein, heme, iron, metal-binding, oxygen transport, phosphoprotein, transport
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: Q9NZD4
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 53728.84

構造登録者

Feng, L.,Jeffrey, P.D.,Shi, Y. (登録日: 2009-07-13, 公開日: 2009-07-28, 最終更新日: 2024-02-21)

主引用文献

Gell, D.A.,Feng, L.,Zhou, S.,Jeffrey, P.D.,Bendak, K.,Gow, A.,Weiss, M.J.,Shi, Y.,Mackay, J.P.
A cis-proline in alpha-hemoglobin stabilizing protein directs the structural reorganization of alpha-hemoglobin.
J.Biol.Chem., 284:29462-29469, 2009

PubMed Abstract: alpha-Hemoglobin (alphaHb) stabilizing protein (AHSP) is expressed in erythropoietic tissues as an accessory factor in hemoglobin synthesis. AHSP forms a specific complex with alphaHb and suppresses the heme-catalyzed evolution of reactive oxygen species by converting alphaHb 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 alphaHb 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, Pro(30), in loop 1 of AHSP. Mutation of Pro(30) to a variety of residue types results in reduced ability to convert alphaHb. In complex with alphaHb, AHSP Pro(30) adopts a cis-peptidyl conformation and makes contact with the N terminus of helix G in alphaHb. Mutations that stabilize the cis-peptidyl conformation of free AHSP, also enhance the alphaHb conversion activity. These findings suggest that AHSP loop 1 can transmit structural changes to the heme pocket of alphaHb, and, more generally, highlight the importance of cis-peptidyl prolyl residues in defining the conformation of regulatory protein loops.

PubMed: 19706593
DOI: 10.1074/jbc.M109.027045

実験手法

X-RAY DIFFRACTION (3.2 Å)