1W09
Solution structure of the cis form of the human alpha-hemoglobin stabilizing protein (AHSP)
Summary for 1W09
| Entry DOI | 10.2210/pdb1w09/pdb |
| Related | 1W0A 1W0B |
| Descriptor | ALPHA-HEMOGLOBIN STABILIZING PROTEIN (1 entity in total) |
| Functional Keywords | ahsp nmr structure, proline cis/trans isomerization, alpha-thalassaemia, alpha-hemoglobin binding, chaperone |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Cytoplasm : Q9NZD4 |
| Total number of polymer chains | 1 |
| Total formula weight | 10862.25 |
| Authors | Santiveri, C.M.,Perez-Canadillas, J.M.,Vadivelu, M.K.,Allen, M.D.,Rutherford, T.J.,Watkins, N.A.,Bycroft, M. (deposition date: 2004-05-25, release date: 2004-06-10, Last modification date: 2024-05-15) |
| Primary citation | 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 Cited by 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: 15178680DOI: 10.1074/jbc.M405016200 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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