Intercellular Signaling by Rhomboids in Eukaryotes and Prokaryotes

Matthew Freeman; Philip Rather

doi:10.1128/9781555815578.ch27

Chapter 27 : Intercellular Signaling by Rhomboids in Eukaryotes and Prokaryotes

Authors: Matthew Freeman¹, Philip Rather²

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Affiliations: 1: MRC Laboratory of Molecular Biology, Hills Rd., Cambridge CB2 0QH, United Kingdom; 2: Department of Microbiology and Immunology, 3001 Rollins Research Bldg., Emory University School of Medicine, Atlanta, Georgia 30322

Content Type: Monograph

Publication Year: 2008

Category: Microbial Genetics and Molecular Biology; Bacterial Pathogenesis

Book DOI: 10.1128/9781555815578

Chapter DOI: 10.1128/9781555815578.ch27

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Abstract:

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.

Citation: Freeman M, Rather P. 2008. Intercellular Signaling by Rhomboids in Eukaryotes and Prokaryotes, p 431-442. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch27

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Intercellular Signaling by Rhomboids in Eukaryotes and Prokaryotes

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FIGURE 1

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.

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FIGURE 1

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FIGURE 2

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.

10.1128/9781555815578/f0435-01_thmb.gif

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FIGURE 2

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.

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