Structural role of the T94I rhodopsin mutation in congenital stationary night blindness.

ABSTRACT: Congenital stationary night blindness (CSNB) is an inherited and non-progressive retinal dysfunction. Here, we present the crystal structure of CSNB-causing T94I^2.61 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 K296^7.43, the site of retinal attachment. This is in stark contrast to the light-activated state of the CSNB-causing G90D^2.57 mutation, where the charged mutation forms a salt bridge with K296^7.43 To find the common denominator between these two functional modifications, we combined our structural data with a kinetic biochemical analysis and molecular dynamics simula

SUBMITTER: Singhal A 

PROVIDER: S-EPMC5048376 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature