4bv0: Difference between revisions
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==High Resolution Structure of Evolved Agonist-bound Neurotensin Receptor 1 Mutant without Lysozyme Fusion== | ==High Resolution Structure of Evolved Agonist-bound Neurotensin Receptor 1 Mutant without Lysozyme Fusion== | ||
<StructureSection load='4bv0' size='340' side='right' caption='[[4bv0]], [[Resolution|resolution]] 3.10Å' scene=''> | <StructureSection load='4bv0' size='340' side='right'caption='[[4bv0]], [[Resolution|resolution]] 3.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4bv0]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4bv0]] 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=4BV0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BV0 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4bv0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bv0 OCA], [https://pdbe.org/4bv0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bv0 RCSB], [https://www.ebi.ac.uk/pdbsum/4bv0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bv0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 25: | Line 25: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Balada | [[Category: Rattus norvegicus]] | ||
[[Category: Batyuk | [[Category: Balada S]] | ||
[[Category: Egloff | [[Category: Batyuk A]] | ||
[[Category: Heine | [[Category: Egloff P]] | ||
[[Category: Hillenbrand | [[Category: Heine P]] | ||
[[Category: Mittl | [[Category: Hillenbrand M]] | ||
[[Category: Plueckthun | [[Category: Mittl P]] | ||
[[Category: Schlinkmann | [[Category: Plueckthun A]] | ||
[[Category: Schuetz | [[Category: Schlinkmann KM]] | ||
[[Category: Scott | [[Category: Schuetz M]] | ||
[[Category: Scott DJ]] | |||
Latest revision as of 14:58, 20 December 2023
High Resolution Structure of Evolved Agonist-bound Neurotensin Receptor 1 Mutant without Lysozyme FusionHigh Resolution Structure of Evolved Agonist-bound Neurotensin Receptor 1 Mutant without Lysozyme Fusion
Structural highlights
FunctionNTR1_RAT Receptor for the tridecapeptide neurotensin. It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. Publication Abstract from PubMedCrystallography 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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