4j2q: Difference between revisions
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==Crystal structure of C-terminally truncated arrestin reveals mechanism of arrestin activation== | |||
<StructureSection load='4j2q' size='340' side='right'caption='[[4j2q]], [[Resolution|resolution]] 3.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4j2q]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J2Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J2Q 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]] 3Å</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=4j2q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j2q OCA], [https://pdbe.org/4j2q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j2q RCSB], [https://www.ebi.ac.uk/pdbsum/4j2q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j2q ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/ARRS_BOVIN ARRS_BOVIN] Note=S-antigen induces autoimmune uveitis. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ARRS_BOVIN ARRS_BOVIN] Arrestin is one of the major proteins of the ros (retinal rod outer segments); it binds to photoactivated-phosphorylated rhodopsin, thereby apparently preventing the transducin-mediated activation of phosphodiesterase. Isoform B plays a role in the phototransduction cascade. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Arrestins interact with G-protein-coupled receptors (GPCRs) to block interaction with G proteins and initiate G-protein-independent signalling. Arrestins have a bi-lobed structure that is stabilized by a long carboxy-terminal tail (C-tail), and displacement of the C-tail by receptor-attached phosphates activates arrestins for binding active GPCRs. Structures of the inactive state of arrestin are available, but it is not known how C-tail displacement activates arrestin for receptor coupling. Here we present a 3.0 A crystal structure of the bovine arrestin-1 splice variant p44, in which the activation step is mimicked by C-tail truncation. The structure of this pre-activated arrestin is profoundly different from the basal state and gives insight into the activation mechanism. p44 displays breakage of the central polar core and other interlobe hydrogen-bond networks, leading to a approximately 21 degrees rotation of the two lobes as compared to basal arrestin-1. Rearrangements in key receptor-binding loops in the central crest region include the finger loop, loop 139 (refs 8, 10, 11) and the sequence Asp 296-Asn 305 (or gate loop), here identified as controlling the polar core. We verified the role of these conformational alterations in arrestin activation and receptor binding by site-directed fluorescence spectroscopy. The data indicate a mechanism for arrestin activation in which C-tail displacement releases critical central-crest loops from restricted to extended receptor-interacting conformations. In parallel, increased flexibility between the two lobes facilitates a proper fitting of arrestin to the active receptor surface. Our results provide a snapshot of an arrestin ready to bind the active receptor, and give an insight into the role of naturally occurring truncated arrestins in the visual system. | |||
Crystal structure of pre-activated arrestin p44.,Kim YJ, Hofmann KP, Ernst OP, Scheerer P, Choe HW, Sommer ME Nature. 2013 Apr 21. doi: 10.1038/nature12133. PMID:23604253<ref>PMID:23604253</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4j2q" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Arrestin 3D structures|Arrestin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bos taurus]] | |||
[[Category: Large Structures]] | |||
[[Category: Choe H-W]] | |||
[[Category: Kim YJ]] | |||
[[Category: Scheerer P]] | |||