1W09

Solution structure of the cis form of the human alpha-hemoglobin stabilizing protein (AHSP)

1W09 の概要

• エントリーDOI: 10.2210/pdb1w09/pdb
• 関連するPDBエントリー: 1W0A 1W0B
• 分子名称: ALPHA-HEMOGLOBIN STABILIZING PROTEIN (1 entity in total)
• 機能のキーワード: ahsp nmr structure, proline cis/trans isomerization, alpha-thalassaemia, alpha-hemoglobin binding, chaperone
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm : Q9NZD4
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 10862.25

構造登録者

Santiveri, C.M.,Perez-Canadillas, J.M.,Vadivelu, M.K.,Allen, M.D.,Rutherford, T.J.,Watkins, N.A.,Bycroft, M. (登録日: 2004-05-25, 公開日: 2004-06-10, 最終更新日: 2024-05-15)

主引用文献

Santiveri, C.M.,Perez-Canadillas, J.M.,Vadivelu, M.K.,Allen, M.D.,Rutherford, T.J.,Watkins, N.A.,Bycroft, M.
NMR structure of the alpha-hemoglobin stabilizing protein: insights into conformational heterogeneity and binding.
J. Biol. Chem., 279:34963-34970, 2004

PubMed Abstract: The structure of alpha-hemoglobin stabilizing protein (AHSP), a molecular chaperone for free alpha-hemoglobin, has been determined using NMR spectroscopy. The protein native state shows conformational heterogeneity attributable to the isomerization of the peptide bond preceding a conserved proline residue. The two equally populated cis and trans forms both adopt an elongated antiparallel three alpha-helix bundle fold but display major differences in the loop between the first two helices and at the C terminus of helix 3. Proline to alanine single point mutation of the residue Pro-30 prevents the cis/trans isomerization. The structure of the P30A mutant is similar to the structure of the trans form of AHSP in the loop 1 region. Both the wild-type AHSP and the P30A mutant bind to alpha-hemoglobin, and the wild-type conformational heterogeneity is quenched upon complex formation, suggesting that just one conformation is the active form. Changes in chemical shift observed upon complex formation identify a binding interface comprising the C terminus of helix 1, the loop 1, and the N terminus of helix 2, with the exposed residues Phe-47 and Tyr-51 being attractive targets for molecular recognition. The characteristics of this interface suggest that AHSP binds at the intradimer alpha1beta1 interface in tetrameric HbA.

PubMed: 15178680
DOI: 10.1074/jbc.M405016200

実験手法

SOLUTION NMR