Membrane immersion allows rhomboid proteases to achieve specificity by reading transmembrane segment dynamics.

ABSTRACT: Rhomboid proteases reside within cellular membranes, but the advantage of this unusual environment is unclear. We discovered membrane immersion allows substrates to be identified in a fundamentally-different way, based initially upon exposing 'masked' conformational dynamics of transmembrane segments rather than sequence-specific binding. EPR and CD spectroscopy revealed that the membrane restrains rhomboid gate and substrate conformation to limit proteolysis. True substrates evolved intrinsically-unstable transmembrane helices that both become unstructured when not supported by the membrane, and facilitate partitioning into the hydrophilic, active-site environment. Accordingly, manipulating substrate and gate dynamics in living cells shifted cleavage sites in a manner incompatible with ex

SUBMITTER: Moin SM 

PROVIDER: S-EPMC3494066 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature