View source for 4bwb


==Structure of Evolved Agonist-bound Neurotensin Receptor 1 Mutant without Lysozyme Fusion==
<StructureSection load='4bwb' size='340' side='right'caption='[[4bwb]], [[Resolution|resolution]] 3.57&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.57&#8491;</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>
</table>
== 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;">
== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4bwb" style="background-color:#fffaf0;"></div>

==See Also==
*[[Neurotensin receptor|Neurotensin receptor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Balada S]]
[[Category: Batyuk A]]
[[Category: Egloff P]]
[[Category: Heine P]]
[[Category: Hillenbrand M]]
[[Category: Mittl P]]
[[Category: Plueckthun A]]
[[Category: Schlinkmann KM]]
[[Category: Scott DJ]]