4h1d

Publication Abstract from PubMed

Rhomboids represent an evolutionarily ancient protease family. Unlike most other proteases, they are polytopic membrane proteins, and specialize in cleaving transmembrane protein substrates. Rhomboid protease's polar active site is embedded in the membrane, and normally closed. For bacterial rhomboid GlpG, it has been proposed that one of the protease's transmembrane helices (S5) can rotate to open a lateral gate, enabling substrate to enter the protease from inside the membrane. Here we study GlpG's conformational change by solving the cocrystal structure of the protease with a mechanism-based inhibitor. We also examine the lateral gating model by crosslinking S5 to a neighboring helix (S2). The crystal structure shows that inhibitor binding displaces a capping loop (L5) from the active site, but causes only minor shifts of the transmembrane helices. Crosslinking S5 and S2, which not only restricts S5's lateral movement, but also prevents substrate from passing between the two helices, does not hinder the protease's ability to cleave a membrane protein substrate in detergent solution and in reconstituted membrane vesicles. Taken together, these data suggest that a large lateral movement of S5 helix is not required for substrate access to rhomboid protease's active site.

Large lateral movement of transmembrane helix S5 is not required for substrate access to the active site of rhomboid intramembrane protease.,Xue Y, Ha Y J Biol Chem. 2013 Apr 22. PMID:23609444^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.