Abstract：
:Computer simulations on a new model of the alpha1b-adrenergic receptor based on the crystal structure of rhodopsin have been combined with experimental mutagenesis to investigate the role of residues in the cytosolic half of helix 6 in receptor activation. Our results support the hypothesis that a salt bridge between the highly conserved arginine (R143(3.50)) of the E/DRY motif of helix 3 and a conserved glutamate (E289(6.30)) on helix 6 constrains the alpha1b-AR in the inactive state. In fact, mutations of E289(6.30) that weakened the R143(3.50)-E289(6.30) interaction constitutively activated the receptor. The functional effect of mutating other amino acids on helix 6 (F286(6.27), A292(6.33), L296(6.37), V299(6.40,) V300(6.41), and F303(6.44)) correlates with the extent of their interaction with helix 3 and in particular with R143(3.50) of the E/DRY sequence.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Greasley PJ,Fanelli F,Rossier O,Abuin L,Cotecchia Sdoi
10.1124/mol.61.5.1025keywords:
subject
Has Abstractpub_date
2002-05-01 00:00:00pages
1025-32issue
5eissn
0026-895Xissn
1521-0111journal_volume
61pub_type
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