4f4o: Difference between revisions
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==Structure of the Haptoglobin-Haemoglobin Complex== | ==Structure of the Haptoglobin-Haemoglobin Complex== | ||
<StructureSection load='4f4o' size='340' side='right' caption='[[4f4o]], [[Resolution|resolution]] 2.90Å' scene=''> | <StructureSection load='4f4o' size='340' side='right'caption='[[4f4o]], [[Resolution|resolution]] 2.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4f4o]] is a 12 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4f4o]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F4O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F4O FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=OXY:OXYGEN+MOLECULE'>OXY | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=OXY:OXYGEN+MOLECULE'>OXY</scene></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=4f4o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f4o OCA], [https://pdbe.org/4f4o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f4o RCSB], [https://www.ebi.ac.uk/pdbsum/4f4o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f4o ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/HBA_PIG HBA_PIG] Involved in oxygen transport from the lung to the various peripheral tissues. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 25: | Line 26: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Sus scrofa]] | [[Category: Sus scrofa]] | ||
[[Category: Andersen | [[Category: Andersen CBF]] | ||
[[Category: Andersen | [[Category: Andersen GR]] | ||
[[Category: Andersen | [[Category: Andersen NH]] | ||
[[Category: Hersleth | [[Category: Hersleth HP]] | ||
[[Category: Moestrup | [[Category: Moestrup SK]] | ||
[[Category: Nielsen | [[Category: Nielsen MJ]] | ||
[[Category: Oliveira | [[Category: Oliveira CLP]] | ||
[[Category: Pedersen | [[Category: Pedersen JS]] | ||
[[Category: Torvund-Jensen | [[Category: Torvund-Jensen M]] | ||
Latest revision as of 11:20, 9 October 2024
Structure of the Haptoglobin-Haemoglobin ComplexStructure of the Haptoglobin-Haemoglobin Complex
Structural highlights
FunctionHBA_PIG Involved in oxygen transport from the lung to the various peripheral tissues. Publication Abstract from PubMedRed cell haemoglobin is the fundamental oxygen-transporting molecule in blood, but also a potentially tissue-damaging compound owing to its highly reactive haem groups. During intravascular haemolysis, such as in malaria and haemoglobinopathies, haemoglobin is released into the plasma, where it is captured by the protective acute-phase protein haptoglobin. This leads to formation of the haptoglobin-haemoglobin complex, which represents a virtually irreversible non-covalent protein-protein interaction. Here we present the crystal structure of the dimeric porcine haptoglobin-haemoglobin complex determined at 2.9 A resolution. This structure reveals that haptoglobin molecules dimerize through an unexpected beta-strand swap between two complement control protein (CCP) domains, defining a new fusion CCP domain structure. The haptoglobin serine protease domain forms extensive interactions with both the alpha- and beta-subunits of haemoglobin, explaining the tight binding between haptoglobin and haemoglobin. The haemoglobin-interacting region in the alphabeta dimer is highly overlapping with the interface between the two alphabeta dimers that constitute the native haemoglobin tetramer. Several haemoglobin residues prone to oxidative modification after exposure to haem-induced reactive oxygen species are buried in the haptoglobin-haemoglobin interface, thus showing a direct protective role of haptoglobin. The haptoglobin loop previously shown to be essential for binding of haptoglobin-haemoglobin to the macrophage scavenger receptor CD163 (ref. 3) protrudes from the surface of the distal end of the complex, adjacent to the associated haemoglobin alpha-subunit. Small-angle X-ray scattering measurements of human haptoglobin-haemoglobin bound to the ligand-binding fragment of CD163 confirm receptor binding in this area, and show that the rigid dimeric complex can bind two receptors. Such receptor cross-linkage may facilitate scavenging and explain the increased functional affinity of multimeric haptoglobin-haemoglobin for CD163 (ref. 4). Structure of the haptoglobin-haemoglobin complex.,Andersen CB, Torvund-Jensen M, Nielsen MJ, de Oliveira CL, Hersleth HP, Andersen NH, Pedersen JS, Andersen GR, Moestrup SK Nature. 2012 Sep 20;489(7416):456-9. doi: 10.1038/nature11369. Epub 2012 Aug 26. PMID:22922649[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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