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Structural studies of membrane proteases

Objective

Proteases are key players in many cellular processes and come in great variety. There are essentially five different catalytic types: serine/threonine, cysteine, aspartic and metallopeptidases. Each type of active site can be found in several different folds, which suggests that active sites have been reinvented multiple times during evolution.
The soluble peptidase folds have been studied in great detail, and in nearly all cases, at least one prototype crystal structure is available. In contrast, there are almost no crystal structures of integral membrane proteases, therefore their mechanistic understanding lies far behind. It is not even clear whether a specific water channel is required to transport a catalytic water molecule to the active site or whether a low concentration of water in the lipid bilayer is sufficient for amide cleavage.
Despite these uncertainties, the combined results of sequence comparisons and biochemical studies suggest that membrane and soluble proteases will probably turn out to have (a) dissimilar folds and (b) similar active sites.
However, there is no good evidence yet for a membrane-embedded cysteine peptidase, and for several membrane protease families the assignment of the catalytic type is controversial, which may be an indication for a novel type of active site. In order to broaden the spectrum of our research we are planning to acquire new skills in membrane protein overexpression, purification and crystallization which we would then apply for structural studies of membrane proteases.

Call for proposal

FP6-2005-MOBILITY-3
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Coordinator

INTERNATIONAL INSTITUTE OF MOLECULAR AND CELL BIOLOGY
EU contribution
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Address
4 Ks. Trojdena St.
WARSAW
Poland

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Participants (2)