Mutation at the entrance of the quinone cavity severely disrupts quinone binding in respiratory complex I.

ABSTRACT: In all resolved structures of complex I, there exists a tunnel-like Q-chamber for ubiquinone binding and reduction. The entrance to the Q-chamber in ND1 subunit forms a narrow bottleneck, which is rather tight and requires thermal conformational changes for ubiquinone to get in and out of the binding chamber. The substitution of alanine with threonine at the bottleneck (AlaThr MUT), associated with 3460/ND1 mtDNA mutation in human complex I, is implicated in Leber's Hereditary Optic Neuropathy (LHON). Here, we show the AlaThr MUT further narrows the Q-chamber entrance cross-section area by almost 30%, increasing the activation free energy barrier of quinone passage by approximately 5 kJ mol^-1. This severely disrupts quinone binding and reduction as quinone passage through the bo

SUBMITTER: Yi JT 

PROVIDER: S-EPMC10663621 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature