Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Home
Search
Quick Search
Advanced
Fulltext
Browse
Collections
Persons
My eDoc
Session History
Login
Name:
Password:
Documentation
Help
Support Wiki
Direct access to
document ID:


          Institute: MPI für medizinische Forschung     Collection: Arbeitsgruppe Zimmermann     Display Documents



  history
ID: 226331.0, MPI für medizinische Forschung / Arbeitsgruppe Zimmermann
Stereochemistry of Glutamate Receptor Agonist Efficacy: Engineering a Dual-Specificity AMPA/Kainate Receptor
Authors:Madden, Dean R.; Cheng, Qing; Thiran, Shalita; Rajan, Shanti; Rigo, Frank; Keinanen, Kari; Reinelt, Stephan; Zimmermann, Herbert; Jayaraman, Vasanthi
Language:English
Date of Publication (YYYY-MM-DD):2004-11-24
Title of Journal:Biochemistry
Journal Abbrev.:Biochem.
Volume:43
Issue / Number:5
Start Page:15838
End Page:15844
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Upon agonist binding, the bilobate ligand-binding domains of the ionotropic glutamate receptors (iGluR) undergo a cleft closure whose magnitude correlates broadly with the efficacy of the agonist. AMPA (-amino-5-methyl-3-hydroxy-4-isoxazolepropionic acid) and kainate are nonphysiological agonists that distinguish between subsets of iGluR. Kainate acts with low efficacy at AMPA receptors. Here we report that the structure-based mutation L651V converts the GluR4 AMPA receptor into a dual-specificity AMPA/kainate receptor fully activated by both agonists. To probe the stereochemical basis of partial agonism, we have also investigated the correlation between agonist efficacy and a series of vibrational and fluorescence spectroscopic signals of agonist binding to the corresponding wild-type and mutant GluR4 ligand-binding domains. Two signals track the extent of channel activation: the maximal change in intrinsic tryptophan fluorescence and the environment of the single non-disulfide bonded C426, which appears to probe the strength of interactions with the ligand -amino group. Both of these signals arise from functional groups that are poised to detect changes in the extent of channel cleft closure and thus provide additional information about the coupling between conformational changes in the ligand-binding domain and activation of the intact receptor.
External Publication Status:published
Document Type:Article
Communicated by:Wulf Kaiser
Affiliations:MPI für medizinische Forschung/Arbeitsgruppe Herbert Zimmermann
MPI für medizinische Forschung/Nachwuchsgruppe Ion Channel Structure
Relations:Has References-URI:http://pubs.acs.org/cgi-bin/pubmed/db=m&form=6&uid=2670628&Dopt=r
Has References-URI:http://pubs.acs.org/cgi-bin/pubmed/db=m&form=6&uid=9804426&Dopt=r
Has References-URI:http://pubs.acs.org/cgi-bin/pubmed/db=m&form=6&uid=2231715&Dopt=r
Has References-URI:http://pubs.acs.org/cgi-bin/pubmed/db=m&form=6&uid=11814354&Dopt=r
Has References-URI:http://pubs.acs.org/cgi-bin/pubmed/db=m&form=6&uid=10814047&Dopt=r
Identifiers:URL:http://pubs.acs.org/cgi-bin/sample.cgi/bichaw/2004... [Abstract HTML]
URL:http://pubs.acs.org/cgi-bin/article.cgi/bichaw/200... [Fulltext HTML]
URL:http://pubs.acs.org/cgi-bin/sample.cgi/bichaw/2004... [Fulltext PDF]
DOI:10.1021/bi048447y S0006-2960(04)08447-8 [DOI]
Full Text:
Sorry, no privileges
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.