Abstract：
:From the deep part of the main ligand-binding crevice, a minor, often shallower pocket extends between the extracellular ends of transmembrane domains (TM)-I, II, III and VII of 7TM receptors. This minor binding pocket is defined by a highly conserved kink in TM-II that is induced by a proline residue located in one of two adjacent positions. Here we argue that this minor binding pocket is important for receptor activation. Functional coupling of the receptors seems to be mediated through the hydrogen bond network located between the intracellular segments of these TMs, with the allosteric interface between TM-II and TM-VII being of particular significance. Importantly, the minor binding pocket, especially the proline-kink in TM-II, is involved in G protein versus arrestin pathway-biased signaling, for example in the angiotensin AT1 system. Consequently, this pocket could be specifically targeted in the development of functionally biased drugs.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Rosenkilde MM,Benned-Jensen T,Frimurer TM,Schwartz TWdoi
10.1016/j.tips.2010.08.006subject
Has Abstractpub_date
2010-12-01 00:00:00pages
567-74issue
12eissn
0165-6147issn
1873-3735pii
S0165-6147(10)00152-5journal_volume
31pub_type
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