Why cells need intramembrane proteases – a mechanistic perspective

  • Kvido Strisovsky
    Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic Prague Czech Republic

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<jats:p>Intramembrane proteases (<jats:styled-content style="fixed-case">IMPR</jats:styled-content>s) cleave transmembrane proteins inside the lipid bilayer. They regulate a growing number of biological processes, and our knowledge about the evolutionary and functional niches these unusual enzymes have filled is slowly unravelling. Although structures of representative members of four <jats:styled-content style="fixed-case">IMPR</jats:styled-content> families have been solved, the mechanism of substrate recognition and cleavage is still poorly understood. Here I offer a view on substrate recognition by <jats:styled-content style="fixed-case">IMPR</jats:styled-content>s from the angle of their biological functions. Zooming in on rhomboid proteases I delineate the emerging principles and areas of contention, and argue that by studying the mechanisms, specificity and natural substrate repertoires of <jats:styled-content style="fixed-case">IMPR</jats:styled-content>s we can understand the properties for which they have been selected in evolution.</jats:p>

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