Preserving the membrane barrier for small molecules during bacterial protein translocation

Polypeptides only need apply Proteins are translocated across the plasma membrane through the SecY channel in bacteria and archaea, and across the endoplasmic reticulum in eukaryotes through the related Sec61 channel. Structural studies have revealed that the channel has an hourglass shape with a narrow constriction formed by a pore ring of amino acids. Eunyong Park and Tom Rapoport address a central question in the field — how does the channel transport polypeptides and yet block the passage of small molecules? Using a novel technique that fills the channels with defined co-translational translocation intermediates in vivo, they show that the SecY channel itself provides a seal for small molecules. Given the sequence conservation of SecY and Sec61 complexes, it is likely that these principles are universal.