Document Detail


Interactions between conserved residues in transmembrane helices 1, 2, and 7 of the thyrotropin-releasing hormone receptor.
MedLine Citation:
PMID:  9115256     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The roles of conserved residues in transmembrane helices (TMs) of G protein-coupled receptors have not been well established. A computer-generated model of the thyrotropin-releasing hormone receptor (TRH-R) indicated that conserved Asp-71 (TM-2) could interact with conserved asparagines 316 (TM-7) and 43 (TM-1). To test this model, we constructed mutant TRH-Rs containing polar or alanine substitutions of these residues. The maximal activities of N43A and N316A TRH-Rs were diminished, whereas D71A (Perlman, J. H., Nussenzveig, D. R., Osman, R., and Gershengorn, M. C. (1992) J. Biol. Chem. 267, 24413-24417) and N43A/N316A TRH-Rs were inactive. Computer models of D71A and N43A/N316A TRH-Rs show similar changes from native TRH-R in their TM bundle conformations. The inactivity and the similarity of the computer models of D71A and N43A/N316A TRH-Rs are consistent with the idea that Asp-71 bridges Asn-43 and Asn-316 and suggest that activity is critically dependent on these interactions. The conservation of these residues suggests these specific interactions involving TMs 1, 2, and 7 may be structurally important for all members of the rhodopsin/beta-adrenergic receptor subfamily of G protein-coupled receptors.
Authors:
J H Perlman; A O Colson; W Wang; K Bence; R Osman; M C Gershengorn
Related Documents :
11182376 - Changing serine-485 to alanine in the opossum parathyroid hormone (pth)/pth-related pep...
8700106 - Alanine scanning mutagenesis of conserved arginine/lysine-arginine/lysine-x-x-arginine/...
18042246 - A profile of the residues in the second extracellular loop that are critical for ligand...
16289886 - The survival of vagal and glossopharyngeal sensory neurons is dependent upon dystonin.
12711626 - Pharmacological discrimination between muscarinic receptor signal transduction cascades...
10540316 - Involvement of the n-methyl-d-aspartate receptor in neuronal cell death induced by cyto...
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  272     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1997 May 
Date Detail:
Created Date:  1997-06-02     Completed Date:  1997-06-02     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  11937-42     Citation Subset:  IM    
Affiliation:
Division of Molecular Medicine, Department of Medicine, Cornell University Medical College and The New York Hospital, New York, New York 10021, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Asparagine
Aspartic Acid
Binding Sites
COS Cells
Computer Simulation
Conserved Sequence
Inositol Phosphates / metabolism
Models, Structural
Mutagenesis, Site-Directed
Point Mutation
Protein Structure, Secondary*
Receptors, Thyrotropin-Releasing Hormone / chemistry*,  metabolism*
Recombinant Proteins / chemistry,  metabolism
Thermodynamics
Thyrotropin-Releasing Hormone / chemistry*,  metabolism*,  pharmacology
Transfection
Grant Support
ID/Acronym/Agency:
DK 02101/DK/NIDDK NIH HHS; DK 43036/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Inositol Phosphates; 0/Receptors, Thyrotropin-Releasing Hormone; 0/Recombinant Proteins; 24305-27-9/Thyrotropin-Releasing Hormone; 56-84-8/Aspartic Acid; 7006-34-0/Asparagine

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


Previous Document:  Phosphorylation and O-glycosylation sites of bovine chromogranin A from adrenal medullary chromaffin...
Next Document:  SAPAPs. A family of PSD-95/SAP90-associated proteins localized at postsynaptic density.