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| | <StructureSection load='6quz' size='340' side='right'caption='[[6quz]], [[Resolution|resolution]] 3.21Å' scene=''> | | <StructureSection load='6quz' size='340' side='right'caption='[[6quz]], [[Resolution|resolution]] 3.21Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6quz]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences] and [http://en.wikipedia.org/wiki/Thema Thema]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QUZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QUZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6quz]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermotoga_maritima_MSB8 Thermotoga maritima MSB8] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QUZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QUZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AGS:PHOSPHOTHIOPHOSPHORIC+ACID-ADENYLATE+ESTER'>AGS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.21Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TM_0287 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243274 THEMA]), TM_0288 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243274 THEMA])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AGS:PHOSPHOTHIOPHOSPHORIC+ACID-ADENYLATE+ESTER'>AGS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=6quz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6quz OCA], [http://pdbe.org/6quz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6quz RCSB], [http://www.ebi.ac.uk/pdbsum/6quz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6quz 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=6quz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6quz OCA], [https://pdbe.org/6quz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6quz RCSB], [https://www.ebi.ac.uk/pdbsum/6quz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6quz ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Y288_THEMA Y288_THEMA] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Synthetic construct sequences]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Thema]] | + | [[Category: Thermotoga maritima MSB8]] |
| - | [[Category: Egloff, P]] | + | [[Category: Egloff P]] |
| - | [[Category: Huerlimann, L M]] | + | [[Category: Huerlimann LM]] |
| - | [[Category: Hutter, C A.J]] | + | [[Category: Hutter CAJ]] |
| - | [[Category: Seeger, M A]] | + | [[Category: Seeger MA]] |
| - | [[Category: Zimmermann, I]] | + | [[Category: Zimmermann I]] |
| - | [[Category: Abc exporter]]
| + | |
| - | [[Category: Abc transporter]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Membrane transporter]]
| + | |
| - | [[Category: Nanobody]]
| + | |
| - | [[Category: Sybody]]
| + | |
| Structural highlights
Function
Y288_THEMA
Publication Abstract from PubMed
ABC exporters harness the energy of ATP to pump substrates across membranes. Extracellular gate opening and closure are key steps of the transport cycle, but the underlying mechanism is poorly understood. Here, we generated a synthetic single domain antibody (sybody) that recognizes the heterodimeric ABC exporter TM287/288 exclusively in the presence of ATP, which was essential to solve a 3.2 A crystal structure of the outward-facing transporter. The sybody binds to an extracellular wing and strongly inhibits ATPase activity by shifting the transporter's conformational equilibrium towards the outward-facing state, as shown by double electron-electron resonance (DEER). Mutations that facilitate extracellular gate opening result in a comparable equilibrium shift and strongly reduce ATPase activity and drug transport. Using the sybody as conformational probe, we demonstrate that efficient extracellular gate closure is required to dissociate the NBD dimer after ATP hydrolysis to reset the transporter back to its inward-facing state.
The extracellular gate shapes the energy profile of an ABC exporter.,Hutter CAJ, Timachi MH, Hurlimann LM, Zimmermann I, Egloff P, Goddeke H, Kucher S, Stefanic S, Karttunen M, Schafer LV, Bordignon E, Seeger MA Nat Commun. 2019 May 21;10(1):2260. doi: 10.1038/s41467-019-09892-6. PMID:31113958[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hutter CAJ, Timachi MH, Hurlimann LM, Zimmermann I, Egloff P, Goddeke H, Kucher S, Stefanic S, Karttunen M, Schafer LV, Bordignon E, Seeger MA. The extracellular gate shapes the energy profile of an ABC exporter. Nat Commun. 2019 May 21;10(1):2260. doi: 10.1038/s41467-019-09892-6. PMID:31113958 doi:http://dx.doi.org/10.1038/s41467-019-09892-6
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