2hbp
From Proteopedia
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| - | [[Image:2hbp.gif|left|200px]]<br /><applet load="2hbp" size="350" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="2hbp" /> | ||
| - | '''Solution Structure of Sla1 Homology Domain 1'''<br /> | ||
| - | == | + | ==Solution Structure of Sla1 Homology Domain 1== |
| + | <StructureSection load='2hbp' size='340' side='right'caption='[[2hbp]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2hbp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HBP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HBP FirstGlance]. <br> | ||
| + | </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=2hbp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hbp OCA], [https://pdbe.org/2hbp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hbp RCSB], [https://www.ebi.ac.uk/pdbsum/2hbp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hbp ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/SLA1_YEAST SLA1_YEAST] Component of the PAN1 actin cytoskeleton-regulatory complex required for the internalization of endosomes during actin-coupled endocytosis. The complex links the site of endocytosis to the cell membrane-associated actin cytoskeleton. Mediates uptake of external molecules and vacuolar degradation of plasma membrane proteins. Plays a role in the proper organization of the cell membrane-associated actin cytoskeleton and promotes its destabilization.<ref>PMID:8335689</ref> <ref>PMID:8756649</ref> <ref>PMID:9008707</ref> <ref>PMID:9128251</ref> <ref>PMID:10198057</ref> <ref>PMID:10594004</ref> <ref>PMID:11940605</ref> <ref>PMID:11950888</ref> <ref>PMID:12388763</ref> <ref>PMID:12237851</ref> <ref>PMID:12814545</ref> <ref>PMID:12734398</ref> <ref>PMID:14761940</ref> <ref>PMID:15525671</ref> <ref>PMID:17286805</ref> | ||
| + | == 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/hb/2hbp_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2hbp ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
Adaptor proteins play important endocytic roles including recognition of internalization signals in transmembrane cargo. Sla1p serves as the adaptor for uptake of transmembrane proteins containing the NPFxD internalization signal, and is essential for normal functioning of the actin cytoskeleton during endocytosis. The Sla1p homology domain 1 (SHD1) within Sla1p is responsible for recognition of the NPFxD signal. This study presents the NMR structure of the NPFxD-bound state of SHD1 and a model for the protein-ligand complex. The alpha+beta structure of the protein reveals an SH3-like topology with a solvent-exposed hydrophobic ligand binding site. NMR chemical shift perturbations and effects of structure-based mutations on ligand binding in vitro define residues that are key for NPFxD binding. Mutations that abolish ligand recognition in vitro also abolish NPFxD-mediated receptor internalization in vivo. Thus, SHD1 is a novel functional domain based on SH3-like topology, which employs a unique binding site to recognize the NPFxD endocytic internalization signal. Its distant relationship with the SH3 fold endows this superfamily with a new role in endocytosis. | Adaptor proteins play important endocytic roles including recognition of internalization signals in transmembrane cargo. Sla1p serves as the adaptor for uptake of transmembrane proteins containing the NPFxD internalization signal, and is essential for normal functioning of the actin cytoskeleton during endocytosis. The Sla1p homology domain 1 (SHD1) within Sla1p is responsible for recognition of the NPFxD signal. This study presents the NMR structure of the NPFxD-bound state of SHD1 and a model for the protein-ligand complex. The alpha+beta structure of the protein reveals an SH3-like topology with a solvent-exposed hydrophobic ligand binding site. NMR chemical shift perturbations and effects of structure-based mutations on ligand binding in vitro define residues that are key for NPFxD binding. Mutations that abolish ligand recognition in vitro also abolish NPFxD-mediated receptor internalization in vivo. Thus, SHD1 is a novel functional domain based on SH3-like topology, which employs a unique binding site to recognize the NPFxD endocytic internalization signal. Its distant relationship with the SH3 fold endows this superfamily with a new role in endocytosis. | ||
| - | + | Structure of Sla1p homology domain 1 and interaction with the NPFxD endocytic internalization motif.,Mahadev RK, Di Pietro SM, Olson JM, Piao HL, Payne GS, Overduin M EMBO J. 2007 Apr 4;26(7):1963-71. Epub 2007 Mar 15. PMID:17363896<ref>PMID:17363896</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 2hbp" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
| - | + | [[Category: Mahadev RK]] | |
| - | [[Category: Mahadev | + | [[Category: Overduin M]] |
| - | [[Category: Overduin | + | |
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Current revision
Solution Structure of Sla1 Homology Domain 1
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