5EN0

Crystal Structure of T94I rhodopsin mutant

5EN0 の概要

• エントリーDOI: 10.2210/pdb5en0/pdb
• 分子名称: Rhodopsin, Guanine nucleotide-binding protein G(t) subunit alpha-3, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• 機能のキーワード: rhodopsin, g protein-coupled receptors, congenital stationary night blindness, constitutive activity, signaling protein
• 由来する生物種: Bos taurus (Bovine); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 42652.98

構造登録者

Singhal, A.,Guo, Y.,Matkovic, M.,Schertler, G.,Deupi, X.,Yan, E.,Standfuss, J. (登録日: 2015-11-08, 公開日: 2016-08-10, 最終更新日: 2024-01-10)

主引用文献

Singhal, A.,Guo, Y.,Matkovic, M.,Schertler, G.,Deupi, X.,Yan, E.C.,Standfuss, J.
Structural role of the T94I rhodopsin mutation in congenital stationary night blindness.
Embo Rep., 17:1431-1440, 2016

PubMed Abstract: Congenital stationary night blindness (CSNB) is an inherited and non-progressive retinal dysfunction. Here, we present the crystal structure of CSNB-causing T94I rhodopsin in the active conformation at 2.3 Å resolution. The introduced hydrophobic side chain prolongs the lifetime of the G protein activating metarhodopsin-II state by establishing a direct van der Waals contact with K296, the site of retinal attachment. This is in stark contrast to the light-activated state of the CSNB-causing G90D mutation, where the charged mutation forms a salt bridge with K296 To find the common denominator between these two functional modifications, we combined our structural data with a kinetic biochemical analysis and molecular dynamics simulations. Our results indicate that both the charged G90D and the hydrophobic T94I mutation alter the dark state by weakening the interaction between the Schiff base (SB) and its counterion E113 We propose that this interference with the tight regulation of the dim light photoreceptor rhodopsin increases background noise in the visual system and causes the loss of night vision characteristic for CSNB patients.

PubMed: 27458239
DOI: 10.15252/embr.201642671

実験手法

X-RAY DIFFRACTION (2.81 Å)