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| | <StructureSection load='4bwb' size='340' side='right'caption='[[4bwb]], [[Resolution|resolution]] 3.57Å' scene=''> | | <StructureSection load='4bwb' size='340' side='right'caption='[[4bwb]], [[Resolution|resolution]] 3.57Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4bwb]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BWB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BWB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4bwb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BWB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BWB FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3zev|3zev]], [[4buo|4buo]], [[4bv0|4bv0]]</td></tr> | + | </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=4bwb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bwb OCA], [https://pdbe.org/4bwb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bwb RCSB], [https://www.ebi.ac.uk/pdbsum/4bwb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bwb 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=4bwb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bwb OCA], [http://pdbe.org/4bwb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bwb RCSB], [http://www.ebi.ac.uk/pdbsum/4bwb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bwb ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NTR1_RAT NTR1_RAT]] Receptor for the tridecapeptide neurotensin. It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. [[http://www.uniprot.org/uniprot/NEUT_RAT NEUT_RAT]] Neurotensin may play an endocrine or paracrine role in the regulation of fat metabolism. It causes contraction of smooth muscle. | + | [[https://www.uniprot.org/uniprot/NTR1_RAT NTR1_RAT]] Receptor for the tridecapeptide neurotensin. It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Crystallography has advanced our understanding of G protein-coupled receptors, but low expression levels and instability in solution have limited structural insights to very few selected members of this large protein family. Using neurotensin receptor 1 (NTR1) as a proof of principle, we show that two directed evolution technologies that we recently developed have the potential to overcome these problems. We purified three neurotensin-bound NTR1 variants from Escherichia coli and determined their X-ray structures at up to 2.75 A resolution using vapor diffusion crystallization experiments. A crystallized construct was pharmacologically characterized and exhibited ligand-dependent signaling, internalization, and wild-type-like agonist and antagonist affinities. Our structures are fully consistent with all biochemically defined ligand-contacting residues, and they represent an inactive NTR1 state at the cytosolic side. They exhibit significant differences to a previously determined NTR1 structure (Protein Data Bank ID code 4GRV) in the ligand-binding pocket and by the presence of the amphipathic helix 8. A comparison of helix 8 stability determinants between NTR1 and other crystallized G protein-coupled receptors suggests that the occupancy of the canonical position of the amphipathic helix is reduced to various extents in many receptors, and we have elucidated the sequence determinants for a stable helix 8. Our analysis also provides a structural rationale for the long-known effects of C-terminal palmitoylation reactions on G protein-coupled receptor signaling, receptor maturation, and desensitization.
| + | |
| - | | + | |
| - | Structure of signaling-competent neurotensin receptor 1 obtained by directed evolution in Escherichia coli.,Egloff P, Hillenbrand M, Klenk C, Batyuk A, Heine P, Balada S, Schlinkmann KM, Scott DJ, Schutz M, Pluckthun A Proc Natl Acad Sci U S A. 2014 Jan 22. PMID:24453215<ref>PMID:24453215</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 4bwb" style="background-color:#fffaf0;"></div>
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| | *[[Neurotensin receptor|Neurotensin receptor]] | | *[[Neurotensin receptor|Neurotensin receptor]] |
| - | == References == | |
| - | <references/> | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Balada, S]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Batyuk, A]] | + | [[Category: Balada S]] |
| - | [[Category: Egloff, P]] | + | [[Category: Batyuk A]] |
| - | [[Category: Heine, P]] | + | [[Category: Egloff P]] |
| - | [[Category: Hillenbrand, M]] | + | [[Category: Heine P]] |
| - | [[Category: Mittl, P]] | + | [[Category: Hillenbrand M]] |
| - | [[Category: Plueckthun, A]] | + | [[Category: Mittl P]] |
| - | [[Category: Schlinkmann, K M]] | + | [[Category: Plueckthun A]] |
| - | [[Category: Scott, D J]] | + | [[Category: Schlinkmann KM]] |
| - | [[Category: G protein coupled receptor]]
| + | [[Category: Scott DJ]] |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
