2itf: Difference between revisions
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==Crystal structure IsdA NEAT domain from Staphylococcus aureus with heme bound== | |||
<StructureSection load='2itf' size='340' side='right'caption='[[2itf]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
| | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2itf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ITF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ITF FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=2itf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2itf OCA], [https://pdbe.org/2itf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2itf RCSB], [https://www.ebi.ac.uk/pdbsum/2itf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2itf ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ISDA_STAA8 ISDA_STAA8] Cell wall-anchored surface receptor that participates in the extraction of heme from oxidized methemoglobin/metHb to enable growth on hemoglobin as a sole iron source (By similarity). Receives heme from IsdB and transfers it to IsdC (By similarity). Also plays a role in the inhibition of host immune response. Protects S.aureus against the bactericidal protease activity of apolactoferrin. Decreases bacterial cellular hydrophobicity, which renders S.aureus resistant to bactericidal human skin fatty acids as well as to beta-defensins and cathelicidin. Also binds fibronectin and chains B-beta and gamma of fibrinogen, promoting clumping of S.aureus with fibrinogen. Involved in adherence of S.aureus to human desquamated nasal epithelial cells and is required for nasal colonization (By similarity).[UniProtKB:A6QG31][UniProtKB:Q7A152] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
== | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/it/2itf_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2itf ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Successful pathogenic organisms have developed mechanisms to thrive under extreme levels of iron restriction. Haem-iron represents the largest iron reservoir in the human body and is a significant source of iron for some bacterial pathogens. NEAT (NEAr Transporter) domains are found exclusively in a family of cell surface proteins in Gram-positive bacteria. Many NEAT domain-containing proteins, including IsdA in Staphylococcus aureus, are implicated in haem binding. Here, we show that overexpression of IsdA in S. aureus enhances growth and an inactivation mutant of IsdA has a growth defect, compared with wild type, when grown in media containing haem as the sole iron source. Furthermore, the haem-binding property of IsdA is contained within the NEAT domain. Crystal structures of the apo-IsdA NEAT domain and in complex with haem were solved and reveal a clathrin adapter-like beta-sandwich fold with a large hydrophobic haem-binding pocket. Haem is bound with the propionate groups directed at the molecular surface and the iron is co-ordinated solely by Tyr(166). The phenol groups of Tyr(166) and Tyr(170) form an H-bond that may function in regulating haem binding and release. An analysis of IsdA structure-sequence alignments indicate that conservation of Tyr(166) is a predictor of haem binding by NEAT domains. | Successful pathogenic organisms have developed mechanisms to thrive under extreme levels of iron restriction. Haem-iron represents the largest iron reservoir in the human body and is a significant source of iron for some bacterial pathogens. NEAT (NEAr Transporter) domains are found exclusively in a family of cell surface proteins in Gram-positive bacteria. Many NEAT domain-containing proteins, including IsdA in Staphylococcus aureus, are implicated in haem binding. Here, we show that overexpression of IsdA in S. aureus enhances growth and an inactivation mutant of IsdA has a growth defect, compared with wild type, when grown in media containing haem as the sole iron source. Furthermore, the haem-binding property of IsdA is contained within the NEAT domain. Crystal structures of the apo-IsdA NEAT domain and in complex with haem were solved and reveal a clathrin adapter-like beta-sandwich fold with a large hydrophobic haem-binding pocket. Haem is bound with the propionate groups directed at the molecular surface and the iron is co-ordinated solely by Tyr(166). The phenol groups of Tyr(166) and Tyr(170) form an H-bond that may function in regulating haem binding and release. An analysis of IsdA structure-sequence alignments indicate that conservation of Tyr(166) is a predictor of haem binding by NEAT domains. | ||
Haem recognition by a Staphylococcus aureus NEAT domain.,Grigg JC, Vermeiren CL, Heinrichs DE, Murphy ME Mol Microbiol. 2007 Jan;63(1):139-49. PMID:17229211<ref>PMID:17229211</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[Category: | <div class="pdbe-citations 2itf" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Staphylococcus aureus]] | [[Category: Staphylococcus aureus]] | ||
[[Category: Grigg | [[Category: Grigg JC]] | ||
[[Category: Heinrichs | [[Category: Heinrichs DE]] | ||
[[Category: Murphy | [[Category: Murphy ME]] | ||
[[Category: Vermeiren | [[Category: Vermeiren CL]] | ||
Latest revision as of 11:14, 30 October 2024
Crystal structure IsdA NEAT domain from Staphylococcus aureus with heme boundCrystal structure IsdA NEAT domain from Staphylococcus aureus with heme bound
Structural highlights
FunctionISDA_STAA8 Cell wall-anchored surface receptor that participates in the extraction of heme from oxidized methemoglobin/metHb to enable growth on hemoglobin as a sole iron source (By similarity). Receives heme from IsdB and transfers it to IsdC (By similarity). Also plays a role in the inhibition of host immune response. Protects S.aureus against the bactericidal protease activity of apolactoferrin. Decreases bacterial cellular hydrophobicity, which renders S.aureus resistant to bactericidal human skin fatty acids as well as to beta-defensins and cathelicidin. Also binds fibronectin and chains B-beta and gamma of fibrinogen, promoting clumping of S.aureus with fibrinogen. Involved in adherence of S.aureus to human desquamated nasal epithelial cells and is required for nasal colonization (By similarity).[UniProtKB:A6QG31][UniProtKB:Q7A152] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedSuccessful pathogenic organisms have developed mechanisms to thrive under extreme levels of iron restriction. Haem-iron represents the largest iron reservoir in the human body and is a significant source of iron for some bacterial pathogens. NEAT (NEAr Transporter) domains are found exclusively in a family of cell surface proteins in Gram-positive bacteria. Many NEAT domain-containing proteins, including IsdA in Staphylococcus aureus, are implicated in haem binding. Here, we show that overexpression of IsdA in S. aureus enhances growth and an inactivation mutant of IsdA has a growth defect, compared with wild type, when grown in media containing haem as the sole iron source. Furthermore, the haem-binding property of IsdA is contained within the NEAT domain. Crystal structures of the apo-IsdA NEAT domain and in complex with haem were solved and reveal a clathrin adapter-like beta-sandwich fold with a large hydrophobic haem-binding pocket. Haem is bound with the propionate groups directed at the molecular surface and the iron is co-ordinated solely by Tyr(166). The phenol groups of Tyr(166) and Tyr(170) form an H-bond that may function in regulating haem binding and release. An analysis of IsdA structure-sequence alignments indicate that conservation of Tyr(166) is a predictor of haem binding by NEAT domains. Haem recognition by a Staphylococcus aureus NEAT domain.,Grigg JC, Vermeiren CL, Heinrichs DE, Murphy ME Mol Microbiol. 2007 Jan;63(1):139-49. PMID:17229211[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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