From Molecular Details of the Interplay between Transmembrane Helices of the Thyrotropin Receptor to General Aspects of Signal Transduction in Family A G-protein-coupled Receptors (GPCRs)

• DOI: 10.1074/jbc.m110.196980
• Publication Date: 2011-05-18T02:06:06Z
• Authors: Gunnar Kleinau; Inna Hoyer; Annika Kreuchwig; Ann-Karin Haas; Claudia Rutz; Jens Furkert; Catherine L. Worth; Gerd Krause; Ralf Schülein
• Keywords: Helix (gastropod)

Transmembrane helices (TMHs) 5 and 6 are known to be important for signal transduction by G-protein-coupled receptors (GPCRs). Our aim was characterize the interface between TMH5 TMH6 of thyrotropin receptor (TSHR) gain molecular insights into aspects regulation. A proline at position 5.50 is highly conserved in family GPCRs causes a twist helix structure. Mutation TSHR-specific alanine (Ala-593⁵·⁵⁰) this resulted 20-fold reduction cell surface expression. This indicates that TSHR might have conformation different from most other forming regular α-helix. Furthermore, linking our own previous data directed mutagenesis with structural information led suggestions distinct pairs interacting residues responsible stabilizing either basal or active state. suggest inactive state constrained core set polar interactions among TMHs 2, 3, 6, 7 contrast stabilized mainly non-polar 6. findings relevant all as supported statistical analysis residue properties vast number GPCR sequences.