The theme of the group concerns protein secretion and membrane protein insertion. We study the Sec complex, essential in every cell in every organism. We investigate the more tractable bacterial system, wherein proteins are driven through the protein channel complex (SecYEG) either co-translationally by associated ribosomes, or post-translationally by associated motor ATPases (SecA) and the trans-membrane proton motive force (PMF).
Our challenge is to address the molecular mechanism of these membrane bound energy transducing transport reactions, and do so using a variety of biophysical and biochemical methods. The machinery can be reconstituted from purified recombinant components, which provides the means for an integrated analysis of their activity, structure and dynamics.
Recent work has determined the first structure of the Sec complex engaged with pre-protein signal sequence (Hizlan et al. 2012; see Figure). Ongoing projects focus on the dynamic mechanism of protein secretion driven through the core SecYEG complex by ATP and the PMF. While newer initaitives concern a 7 component ‘holo’-complex capable of both post-translational secretion and co-translational membrane protein insertion.
William Allen, Sarah Whitehouse, Joanna Komar and Robin Corey.
Hizlan D, A Robson, Whitehouse S, Gold VA, Vonck J, Mills D, Kühlbrandt W, Collinson I. (2012) Structure of the SecY Complex Unlocked by a Preprotein Mimic. Cell Reports. 1: 21-28.
Reggie L, Lopez JJ, Collinson I, Glaubitz C, Lorch M. (2011) Dynamic nuclear polarization-enhanced solid-state NMR of a 13C-labeled signal peptide bound to lipid-reconstituted Sec translocon. Journal of the American Chemical Society. 133:19084-6.
Deville K, Gold VA, Robson A, Whitehouse S, Sessions RB, Baldwin SA, Radford SE, Collinson I. (2011) The oligomeric state and arrangement of the active bacterial translocon. Journal of Biological Chemistry. 286:4659-69.
Gold VA, Robson A, Bao H, Romantsov T, Duong F, Collinson I. (2010) The action of cardiolipin on the bacterial translocon. PNAS USA. 107:10044-10049.