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    
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.
J H Perlman; A O Colson; W Wang; K Bence; R Osman; M C Gershengorn
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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    
Division of Molecular Medicine, Department of Medicine, Cornell University Medical College and The New York Hospital, New York, New York 10021, USA.
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MeSH Terms
Amino Acid Sequence
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
Thyrotropin-Releasing Hormone / chemistry*,  metabolism*,  pharmacology
Grant Support
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

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