Balanced internal hydration discriminates substrate binding to respiratory complex I

Publication date: Available online 4 June 2019Source: Biochimica et Biophysica Acta (BBA) - BioenergeticsAuthor(s): Murilo Hoias Teixeira, Guilherme Menegon ArantesAbstractMolecular recognition of the amphiphilic electron carrier ubiquinone (Q) by respiratory complexes is a fundamental part of electron transfer chains in mitochondria and many bacteria. The primary respiratory complex I binds Q in a long and narrow protein chamber to catalyse its reduction. But, the binding mechanism and the role of chamber hydration in substrate selectivity and stability are unclear. Here, large-scale atomistic molecular dynamics simulations and estimated free energy profiles are used to characterize in detail the binding mechanism to complex I of Q with short and with long isoprenoid tails. A highly stable binding site with two different poses near the chamber exit and a secondary reactive site near the N2 iron-sulfur cluster are found which may lead to an alternative Q redox chemistry and help to explain complex I reactivity. The binding energetics depends mainly on polar interactions of the Q-head and on the counterbalanced hydration of Q-tail isoprenoid units and hydrophobic residues inside the protein chamber. Selectivity upon variation of tail length arises by shifting the hydration balance. This internal hydration mechanism may have implications for binding of amphiphilic molecules to cavities in other membrane proteins.Graphical Abstract

Source: Biochimica et Biophysica Acta (BBA) Bioenergetics - June 4, 2019 Category: Biochemistry Source Type: research