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Specific cardiolipin-SecY interactions are required for proton-motive force stimulation of protein secretion

Abstract: The transport of proteins across or into membranes is a vital biological process, achieved in every cell by the conserved Sec machinery. In bacteria, SecYEG combines with the SecA motor protein for secretion of preproteins across the plasma membrane, powered by ATP hydrolysis and the transmembrane proton-motive force (PMF). The activities of SecYEG and SecA are modulated by membrane lipids, particularly cardiolipin (CL), a specialized phospholipid known to associate with a range of energy-transducing machines. Here, we identify two specific CL binding sites on the Thermotoga maritima SecA-SecYEG complex, through application of coarse-grained molecular dynamics simulations. We validate the computational data and demonstrate the conserved nature of the binding sites using in vitro mutagenesis, native mass spectrometry, biochemical analysis, and fluorescence spectroscopy of Escherichia coli SecYEG. The results show that the two sites account for the preponderance of functional CL binding to SecYEG, and mediate its roles in ATPase and protein transport activity. In addition, we demonstrate an important role for CL in the conferral of PMF stimulation of protein transport. The apparent transient nature of the CL interaction might facilitate proton exchange with the Sec machinery, and thereby stimulate protein transport, by a hitherto unexplored mechanism. This study demonstrates the power of coupling the high predictive ability of coarse-grained simulation with experimental analyses, toward investigation of both the nature and functional implications of protein-lipid interactions.

 Fuente: Proc Natl Acad Sci U S A. 2018 Jul 31; 115(31):7967-7972

Editorial: National Academy of Sciences

 Fecha de publicación: 31/07/2018

Nº de páginas: 6

Tipo de publicación: Artículo de Revista

 DOI: 10.1073/pnas.1721536115

ISSN: 0027-8424,1091-6490

Url de la publicación: https://dx.doi.org/10.1073/pnas.1721536115

Autores/as

COREY, ROBIN A.

PYLE, EUAN

ALLEN, WILLIAM J.

WATKINS, DANIEL W.

CASIRAGHI, MARINA

MIROUX, BRUNO

COLLINSON, IAN