@article{Identification:1631,
      recid = {1631},
      author = {Anghel, Stefan Andrei},
      title = {Identification of a Superfamily of Membrane Protein  Biogenesis Factors},
      publisher = {University of Chicago},
      school = {Ph.D.},
      address = {2018-06},
      pages = {136},
      abstract = {Cells possess specialized machinery to direct the  insertion of membrane proteins into the lipid bilayer. In  all organisms, the Sec61/SecYEG channel inserts most  membrane proteins into the membrane in concert with various  accessory subunits. Additionally, other membrane protein  insertion systems have been described. In bacteria, the  essential protein YidC inserts certain proteins into the  plasma membrane. Eukaryotic orthologs of YidC are present  in the mitochondrial inner membrane and the chloroplast  thylakoid membrane (where they are called Oxa1 and Alb3  respectively) but no homologs have been described outside  the endosymbiotic organelles. In eukaryotes, the Get1/2  complex inserts a subset of proteins with a single  transmembrane domain at their C-terminus, but whether this  pathway is conserved in prokaryotes is also unclear. Here,  I present evidence that bacterial YidC and eukaryotic Get1  are both members of a superfamily of membrane protein  biogenesis factors which I refer to as the Oxa1  superfamily. This superfamily includes a group of archaeal  proteins annotated as DUF106, and two eukaryotic proteins  named EMC3 and TMCO1. All superfamily members share a core  membrane topology and structural fold in addition to key  functional features. Archaeal superfamily members, like  bacterial YidC, interact specifically with ribosomes  translating a YidC substrate. Of the eukaryotic proteins, I  show that the previously poorly understood TMCO1 protein  functions in membrane protein biogenesis. TMCO1 associates  with ribosomes translating multipass membrane proteins and  functions in a complex with the Sec61 channel, some  translocon accessory components and a group of poorly  understood protein quality control factors. This work  establishes a new paradigm for the evolution of membrane  protein biogenesis factors and defines a biochemical  function for TMCO1, paving the way for future mechanistic  analysis of this novel pathway.},
      url = {http://knowledge.uchicago.edu/record/1631},
      doi = {https://doi.org/10.6082/uchicago.1631},
}