Full text loading...
Chapter 27 : Intercellular Signaling by Rhomboids in Eukaryotes and Prokaryotes
Category: Microbial Genetics and Molecular Biology; Bacterial Pathogenesis
Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase
The rhomboid family of intramembrane serine proteases controls a variety of functions in both eukaryotes and prokaryotes. The rhomboid proteins were originally identified in Drosophila, where they are required for growth factor signal generation. However, in recent years, a number of diverse functions for the rhomboid proteins have been identified. These functions include (i) the cleavage of TatA, a membrane-bound component of the twin arginine transport system that is required for cell-cell signaling in a prokaryote; (ii) regulating mitochondrial membrane fusion in Saccharomyces; and (iii) cleavage of cell surface adhesions in apicomplexan parasites. Recent biochemical analyses combined with crystallography studies have confirmed these enzymes use a Ser-His catalytic dyad. Moreover, the active-site serine of these enzymes is embedded within the membrane bilayer, and access to water in the membrane is mediated by a hydrophilic cavity that extends from the extracellular environment to the active-site serine. This chapter expands on each of the above themes and provides some future directions for the analysis of this novel class of membrane proteases.
Drosophila Rhomboid-1 has seven transmembrane domains, and its active site comprises residues within the plane of the lipid bilayer. It cleaves its substrate, Spitz, within the TMD. This allows the extracellular domain of Spitz to be released from the cell, so that it can activate the EGF receptor in neighboring cells. Catalytic and other key residues are shown.
Alignment of the N-terminal region of TatA proteins from P. mirabilis, E. coli, and P. stuartii. The arrowhead designates the site of AarA-dependent cleavage for the P. stuartiiTatA protein.