Structure and function of the membrane insertase YidC

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A key feature of membrane proteins is that, in addition to being synthesized, they must assemble properly in the membrane. In bacteria, this membrane protein assembly process is catalyzed by the inner membrane protein YidC. YidC is an evolutionarily conserved membrane protein also found in mitochondrial and chloroplast membranes. YidC can work as a single enzyme or in concert with the SecYEG translocation channel that inserts most proteins into the inner membrane in E. coli. Unanswered questions regarding YidC are: how does this protein bind to substrates during membrane biogenesis, how does it assemble transmembrane segments to promote folding of membrane proteins, and what is the molecular structure of this membrane protein insertase? This proposal has three main goals: (1) defining the substrate binding pocket, (2) determining the YidC function for Sec-dependent proteins and (3) defining the molecular structure of YidC. Solving these aspects will provide important information on how YidC functions as a site for insertion and assembly of membrane proteins.