Document Detail

Distinct properties of glycine receptor β+/α- interface: unambiguously characterizing heteromeric interface reconstituted in homomeric protein.
MedLine Citation:
PMID:  22535951     Owner:  NLM     Status:  MEDLINE    
The glycine receptor (GlyR) exists either in homomeric α or heteromeric αβ forms. Its agonists bind at extracellular subunit interfaces. Unlike subunit interfaces from the homomeric α GlyR, subunit interfaces from the heteromeric αβ GlyR have not been characterized unambiguously because of the existence of multiple types of interface within single receptors. Here, we report that, by reconstituting β+/α- interfaces in a homomeric GlyR (αChb+a- GlyR), we were able to functionally characterize the αβ GlyR β+/α- interfaces. We found that the β+/α- interface had a higher agonist sensitivity than that of the α+/α- interface. This high sensitivity was contributed primarily by loop A. We also found that the β+/α- interface differentially modulates the agonist properties of glycine and taurine. Using voltage clamp fluorometry, we found that the conformational changes induced by glycine binding to the β+/α- interface were different from those induced by glycine binding to the α+/α- interface in the α GlyR. Moreover, the distinct conformational changes found at the β+/α- interface in the αChb+a- GlyR were also found in the heteromeric αβ GlyR, which suggests that the αChb+a- GlyR reconstitutes structural components and recapitulates functional properties, of the β+/α- interface in the heteromeric αβ GlyR. Our investigation not only provides structural and functional information about the GlyR β+/α- interface, which could direct GlyR β+/α- interface-specific drug design, but also provides a general methodology for unambiguously characterizing properties of specific protein interfaces from heteromeric proteins.
Qiang Shan; Lu Han; Joseph W Lynch
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-25
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-18     Completed Date:  2012-08-24     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  21244-52     Citation Subset:  IM    
Brain and Mind Research Institute, University of Sydney, Sydney, New South Wales 2050, Australia.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Glycine / chemistry,  genetics,  metabolism*
HEK293 Cells
Protein Multimerization / physiology*
Protein Structure, Quaternary
Receptors, Glycine / chemistry,  genetics,  metabolism*
Structure-Activity Relationship
Xenopus laevis
Reg. No./Substance:
0/GLRB protein, human; 0/Receptors, Glycine; 56-40-6/Glycine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Complete genome sequence of Paenibacillus mucilaginosus 3016, a bacterium functional as microbial fe...
Next Document:  Proteomic and metabolomic analyses of mitochondrial complex I-deficient mouse model generated by spo...