Award details

Structural and functional analysis of a ubiquitous protein translocation apparatus

Reference	BB/C503538/1
Principal Investigator / Supervisor	Professor Ian Collinson
Co-Investigators / Co-Supervisors	Professor R Brady, Dr Rebecca Tranter
Institution	University of Bristol
Department	Biochemistry
Funding type	Research
Value (£)	242,117
Status	Completed
Type	Research Grant
Start date	01/11/2004
End date	31/12/2007
Duration	38 months

Abstract

The core related Sec61 (eukaryotes) or SecY (bacteria/archaea) complexes reside, respectively, in ER and cytosolic membranes and provide the major route for protein translocation. The associated partners of the channels that drive translocation differ according to the organism and the substrate protein. Eukaryotes prefer a co-translational mechanism, whereby ribosomes attach to the Sec complex and drive translocation as the protein is synthesised. Bacteria have the same pathway, but predominantly utilise a post-translational association of an ATPase SecA, which delivers unfolded substrate protein to the membrane and drives translocation in multiple steps of ATP hydrolysis. The atomic structure shows that a monomer of the Sec complex (SecYEG/SecYEbeta) forms the protein conducting channel, in a closed state. The heterotrimer forms a narrow channel at the centre, which essentially constricts the membrane like an hour-glass. The channel is held in a closed conformation by a plug in the centre. This channel must open to enable the passage of translocating polypeptide through or into the membrane. The two structures provide static pictures of two different and closed translocation complexes. Therefore, the aim of the project will be to obtain new structural information of activated forms of the channel. This will be done through an analysis of complexes together with an engaged translocation partner or substrate. We have been able to make various complexes that we believe will have interesting structures pertinent to these goals. Complexes can be made with SecYEG and signal sequences of substrate protein. In addition, partner proteins (SecA and Ribosomes) have also been produced and bound to the channel. All of these new preparations will be used in a structural and functional investigation. The objective is to obtain new information about different conformations of the reaction cycle, in order that we can understand in more detail the chemistry and dynamics that bring about protein translocation.

Summary

unavailable

Committee	Closed Committee - Biomolecular Sciences (BMS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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