English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  Agonist-induced isomerization in a glutamate receptor ligand-binding domain: a kinetic and mutagenetic analysis

Abele, R., Keinänen, K., & Madden, D. R. (2000). Agonist-induced isomerization in a glutamate receptor ligand-binding domain: a kinetic and mutagenetic analysis. The Journal of Biological Chemistry, 275, 21355-21363. doi:10.1074/jbc.M909883199.

Item is

Basic

show hide
Genre: Journal Article
Alternative Title : Agonist-induced isomerization in a glutamate receptor ligand-binding domain: a kinetic and mutagenetic analysis

Files

show Files
hide Files
:
JBiolChem_275_2000_21355.pdf (Any fulltext), 269KB
 
File Permalink:
-
Name:
JBiolChem_275_2000_21355.pdf
Description:
-
Visibility:
Restricted (Max Planck Institute for Medical Research, MHMF; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show
hide
Description:
-
Description:
-

Creators

show
hide
 Creators:
Abele, Rupert1, Author              
Keinänen, Kari, Author
Madden, Dean R.1, Author              
Affiliations:
1Max Planck Research Group Ion Channel Structure (Dean R. Madden), Max Planck Institute for Medical Research, Max Planck Society, ou_1497725              

Content

show
hide
Free keywords: -
 Abstract: Agonist binding to glutamate receptor ion channels occurs within an extracellular domain (S1S2) that retains ligand affinity when expressed separately. S1S2 is homologous to periplasmic binding proteins, and it has been proposed that a Venus flytrap-style cleft closure triggers opening of glutamate receptor ion channels. Here we compare the kinetics of S1S2-agonist binding to those of the periplasmic binding proteins and show that the reaction involves an initial rapid association, followed by slower conformational changes that stabilize the complex: "docking" followed by "locking." The motion detected here reflects the mechanism by which the energy of glutamate binding is converted into protein conformational changes within S1S2 alone. In the intact channel, these load-free conformational changes are harnessed and possibly modified as the agonist binding reaction is used to drive channel opening and subsequent desensitization. Using mutagenesis, key residues in each step were identified, and their roles were interpreted in light of a published S1S2 crystal structure. In contrast to the Venus flytrap proposal, which focuses on motion between the two lobes as the readout for agonist binding, we argue that smaller, localized conformational rearrangements allow agonists to bridge the cleft, consistent with published hydrodynamic measurements.

Details

show
hide
Language(s): eng - English
 Dates: 2000-03-201999-12-102000-03-202000-03-282000-07-14
 Publication Status: Published in print
 Pages: 9
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: The Journal of Biological Chemistry
  Other : JBC
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Baltimore, etc. : American Society for Biochemistry and Molecular Biology [etc.]
Pages: - Volume / Issue: 275 Sequence Number: - Start / End Page: 21355 - 21363 Identifier: ISSN: 0021-9258
CoNE: https://pure.mpg.de/cone/journals/resource/954925410826_1