|
|
| (4 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==Solution structure of the P30-trans form of Alpha Hemoglobin Stabilizing Protein (AHSP)== | | ==Solution structure of the P30-trans form of Alpha Hemoglobin Stabilizing Protein (AHSP)== |
| - | <StructureSection load='1xzy' size='340' side='right' caption='[[1xzy]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1xzy' size='340' side='right'caption='[[1xzy]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1xzy]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XZY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1XZY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1xzy]] 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=1XZY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XZY FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1w09|1w09]], [[1w0a|1w0a]], [[1w0b|1w0b]]</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AHSP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=1xzy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xzy OCA], [https://pdbe.org/1xzy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xzy RCSB], [https://www.ebi.ac.uk/pdbsum/1xzy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xzy ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xzy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xzy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1xzy RCSB], [http://www.ebi.ac.uk/pdbsum/1xzy PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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 == |
| Line 17: |
Line 17: |
| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 1xzy" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Line 22: |
Line 23: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Feng, L]] | + | [[Category: Large Structures]] |
| - | [[Category: Gell, D A]] | + | [[Category: Feng L]] |
| - | [[Category: Kong, Y]] | + | [[Category: Gell DA]] |
| - | [[Category: Lee, C]] | + | [[Category: Kong Y]] |
| - | [[Category: Mackay, J P]] | + | [[Category: Lee C]] |
| - | [[Category: Shi, Y]] | + | [[Category: Mackay JP]] |
| - | [[Category: Weiss, M J]] | + | [[Category: Shi Y]] |
| - | [[Category: Zhou, S]] | + | [[Category: Weiss MJ]] |
| - | [[Category: Chaperone]]
| + | [[Category: Zhou S]] |
| - | [[Category: Helical bundle]]
| + | |
| - | [[Category: Three-helix bundle]]
| + | |
| 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
Hemoglobin A (HbA), the oxygen delivery system in humans, comprises two alpha and two beta subunits. Free alpha-hemoglobin (alphaHb) is unstable, and its precipitation contributes to the pathophysiology of beta thalassemia. In erythrocytes, the alpha-hemoglobin stabilizing protein (AHSP) binds alphaHb and inhibits its precipitation. The crystal structure of AHSP bound to Fe(II)-alphaHb reveals that AHSP specifically recognizes the G and H helices of alphaHb through a hydrophobic interface that largely recapitulates the alpha1-beta1 interface of hemoglobin. The AHSP-alphaHb interactions are extensive but suboptimal, explaining why beta-hemoglobin can competitively displace AHSP to form HbA. Remarkably, the Fe(II)-heme group in AHSP bound alphaHb is coordinated by the distal but not the proximal histidine. Importantly, binding to AHSP facilitates the conversion of oxy-alphaHb to a deoxygenated, oxidized [Fe(III)], nonreactive form in which all six coordinate positions are occupied. These observations reveal the molecular mechanisms by which AHSP stabilizes free alphaHb.
Molecular mechanism of AHSP-mediated stabilization of alpha-hemoglobin.,Feng L, Gell DA, Zhou S, Gu L, Kong Y, Li J, Hu M, Yan N, Lee C, Rich AM, Armstrong RS, Lay PA, Gow AJ, Weiss MJ, Mackay JP, Shi Y Cell. 2004 Nov 24;119(5):629-40. PMID:15550245[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
- ↑ Feng L, Gell DA, Zhou S, Gu L, Kong Y, Li J, Hu M, Yan N, Lee C, Rich AM, Armstrong RS, Lay PA, Gow AJ, Weiss MJ, Mackay JP, Shi Y. Molecular mechanism of AHSP-mediated stabilization of alpha-hemoglobin. Cell. 2004 Nov 24;119(5):629-40. PMID:15550245 doi:10.1016/j.cell.2004.11.025
|
