▶Subject: The understanding of visual signal transduction from X-ray structure analysis of a protein

▶Speaker: Yongju Kim Ph.D. (Institut f?r Med. Physik und Biophysik, Berlin)

 

▶Date: 2:00PM/February/7(Fri)/2014

 

▶Place: Life Science Bldg. #104

 *Abctract
G-protein-coupled receptors (GPCRs) are seven transmembrane helix proteins that transduce signals into living cells by binding extracellular ligands and coupling to intracellular heterotrimeric G proteins (Gαβγ). The photoreceptor rhodopsin couples to transducin and bears its ligand 11-cis-retinal covalently bound via a protonated Schiff base to the opsin apoprotein. Absorption of a photon causes retinal cis/trans isomerization and generates the agonist all-trans-retinal in situ. After early photoproducts, the active G-protein-binding intermediate metarhodopsin II (Meta?II) is formed, in which the retinal Schiff base is still intact but deprotonated. In the Meta?II structures, the electron density from the retinal ligand seamlessly continues into the Lys?296 side chain, reflecting proper formation of the Schiff base linkage. The retinal is in a relaxed conformation and almost undistorted compared with pure crystalline all-trans-retinal. By comparison with early photoproducts we propose how retinal translocation and rotation induce the gross conformational changes characteristic for Meta?II. The structures can now serve as models for the large GPCR family.
Arrestins interact with GPCRs to block interaction with G proteins and initiate G-protein-independent signalling. Arrestins have a bi-lobed structure that is stabilized by a long carboxy-terminal tail (C-tail), and displacement of the C-tail by receptor-attached phosphates activates arrestins for binding active GPCRs. The p44 protein is a splice variant mutant of arrestin lacking the last 35 residues of the C-tail and the final residue replaced by a single Ala. The structure of the pre-activated arrestin, p44 is profoundly different from the basal state and gives insight into the activation mechanism. p44 displays breakage of the central polar core and other interlobe hydrogen-bond networks, leading to a ∼21° rotation of the two lobes as compared to basal arrestin-1. Rearrangements in key receptor-binding loops in the central crest region include the finger loop, loop 139 and the sequence Asp?296-Asn?305 (or gate loop), here identified as controlling the polar core

▶Inquiry: Prof. Joo-Yeon Yoo (279-2346)