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| | ==Solution structure of the trans form of the human alpha-hemoglobin stabilizing protein (AHSP)== | | ==Solution structure of the trans form of the human alpha-hemoglobin stabilizing protein (AHSP)== |
| - | <StructureSection load='1w0a' size='340' side='right'caption='[[1w0a]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1w0a' size='340' side='right'caption='[[1w0a]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1w0a]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W0A FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1w0a]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W0A FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1w09|1w09]], [[1w0b|1w0b]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1w0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w0a OCA], [https://pdbe.org/1w0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w0a RCSB], [https://www.ebi.ac.uk/pdbsum/1w0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w0a ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1w0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w0a OCA], [https://pdbe.org/1w0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w0a RCSB], [https://www.ebi.ac.uk/pdbsum/1w0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w0a ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/AHSP_HUMAN AHSP_HUMAN]] Acts as a chaperone to prevent the harmful aggregation of alpha-hemoglobin during normal erythroid cell development. Specifically protects free alpha-hemoglobin from precipitation. It is predicted to modulate pathological states of alpha-hemoglobin excess such as beta-thalassemia.<ref>PMID:12066189</ref>
| + | [https://www.uniprot.org/uniprot/AHSP_HUMAN AHSP_HUMAN] Acts as a chaperone to prevent the harmful aggregation of alpha-hemoglobin during normal erythroid cell development. Specifically protects free alpha-hemoglobin from precipitation. It is predicted to modulate pathological states of alpha-hemoglobin excess such as beta-thalassemia.<ref>PMID:12066189</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Allen, M D]] | + | [[Category: Allen MD]] |
| - | [[Category: Bycroft, M]] | + | [[Category: Bycroft M]] |
| - | [[Category: Perez-Canadillas, J M]] | + | [[Category: Perez-Canadillas JM]] |
| - | [[Category: Rutherford, T J]] | + | [[Category: Rutherford TJ]] |
| - | [[Category: Santiveri, C M]] | + | [[Category: Santiveri CM]] |
| - | [[Category: Vadivelu, M K]] | + | [[Category: Vadivelu MK]] |
| - | [[Category: Watkins, N A]] | + | [[Category: Watkins NA]] |
| - | [[Category: Ahsp nmr structure]]
| + | |
| - | [[Category: Alpha-hemoglobin binding]]
| + | |
| - | [[Category: Alpha-thalassaemia]]
| + | |
| - | [[Category: Chaperone]]
| + | |
| - | [[Category: Proline cis/trans isomerization]]
| + | |
| Structural highlights
Function
AHSP_HUMAN Acts as a chaperone to prevent the harmful aggregation of alpha-hemoglobin during normal erythroid cell development. Specifically protects free alpha-hemoglobin from precipitation. It is predicted to modulate pathological states of alpha-hemoglobin excess such as beta-thalassemia.[1]
Publication Abstract from PubMed
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.
NMR structure of the alpha-hemoglobin stabilizing protein: insights into conformational heterogeneity and binding.,Santiveri CM, Perez-Canadillas JM, Vadivelu MK, Allen MD, Rutherford TJ, Watkins NA, Bycroft M J Biol Chem. 2004 Aug 13;279(33):34963-70. Epub 2004 Jun 3. PMID:15178680[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kihm AJ, Kong Y, Hong W, Russell JE, Rouda S, Adachi K, Simon MC, Blobel GA, Weiss MJ. An abundant erythroid protein that stabilizes free alpha-haemoglobin. Nature. 2002 Jun 13;417(6890):758-63. PMID:12066189 doi:http://dx.doi.org/10.1038/nature00803
- ↑ Santiveri CM, Perez-Canadillas JM, Vadivelu MK, Allen MD, Rutherford TJ, Watkins NA, Bycroft M. NMR structure of the alpha-hemoglobin stabilizing protein: insights into conformational heterogeneity and binding. J Biol Chem. 2004 Aug 13;279(33):34963-70. Epub 2004 Jun 3. PMID:15178680 doi:10.1074/jbc.M405016200
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