1. Rhomboid Proteases: Familiar Features in Unfamiliar Phases
Bilal Amarneh, Robert B. Rawson 
Molecular Cell 
Volume 36, Issue 6, Pages (December 2009)
DOI: /j.molcel
Copyright © 2009 Elsevier Inc. Terms and Conditions

2. Figure 1 Two Possible Mechanisms for Cleavage by Rhomboid
An unanswered question for the I-CLiPs is how their substrates gain access to the active site. In rhomboid, this lies close to the middle of the bilayer. While the models shown here are distinct, many of their features are not mutually exclusive. In each, for example, some unwinding of the substrate helix is a likely prerequisite to hydrolysis of the scissile bond, irrespective of the precise sequence of events in which it occurs. This likely explains the requirement for helix-destabilizing residues in the substrate. In the first model, designated “lateral entry,” movement of two helices in rhomboid opens up the enzyme to allow the substrate helix access to the active site. No specific interaction between the active site residues and residues flanking the scissile bond is invoked by this model, although it is compatible with such a notion. In the second model, here termed “exosite,” the substrate helix interacts with the enzyme at a site distinct from the active site. Partial unwinding of the helix permits the scissile bond access to the active site via the membrane-solvent interface. In the active site, typical enzyme-substrate interactions specify which bond is to be cleaved. Unwinding of the substrate helix may be facilitated by the fact that the enzyme resides in a locally thin domain of the membrane (Bondar et al., 2009; Wang et al., 2007). This is shown here for the second model, although this could be a feature of either. As the substrate approaches the enzyme, sequences normally lying within the bilayer may be forced out, potentiating helix unwinding. In this abstract schematic, the substrate helix is indicated by the green cylinder, and rhomboid is shown in red. The bilayer is gold. The “x” represents the scissile bond. The active site is indicated by arrow.
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2009 Elsevier Inc. Terms and Conditions