A Novel and Ubiquitous System for Membrane Targeting and Secretion of Cofactor-Containing Proteins

Abstract

We report the identification of the proteins encoded by the mttABC operon (formerly yigTUW), which mediate a novel Sec-independent membrane targeting and translocation system in Escherichia coli that interacts with cofactor-containing redox proteins having a S/TRRXFLK "twin arginine" leader motif. A pleiotropic-negative mutant in mttA prevents the periplasmic localization of twin arginine redox enzymes, including nitrate reductase (NapA) and trimethylamine N-oxide reductase (TorA). The mutation also prevents the correct localization of the integral membrane molybdoenzyme dimethylsulfoxide reductase (DmsABC). The DmsA subunit has a twin arginine leader. Proteins with a Sec-dependent leader or which assemble spontaneously in the membrane are not affected by this mutation. MttA, B, and C are members of a large family of related sequences extending from archaebacteria to higher eukaryotes.

Functional analysis of a Campylobacter jejuni alkaline phosphatase secreted via the Tat export machinery

“…Genome analysis predicts at least 11 putative Tat substrates in C. jejuni strain NCTC 11168 (Table 3) (Dilks et al, 2003). Besides PhoA Cj , we provide evidence that nitrate reductase NapA, a well-documented Tat substrate in other bacterial species (Ding & Christie, 2003;Lavander et al, 2006;Weiner et al, 1998), requires the Tat system of C. jejuni (Fig. 3d).…”

Assembly pathway of a bacterial complex iron sulfur molybdoenzyme

“…The twin-arginine translocase (Tat) system is the purported protein-conducting channel used by enzymes that exhibit cytoplasmic cofactor insertion and subsequent membrane localization (5)(6)(7). Proteins that utilize the Tat pathway are characterized by two defining features: (i) they contain a consensus S/T-R-R-x-F-L-K twin arginine (RR) motif in their N-terminal leader peptide sequence (RR-leader); and (ii) they are usually translocated across the cytoplasmic membrane as an active and folded holoenzyme (8)(9)(10).…”

The identification of exported proteins with gene fusions to invasin

“…Furthermore, type III exported effector molecules are often genetically linked to their export apparatus, rendering their identification straight forward once an export apparatus is identified. Quite recently, a novel and ubiquitous system for membrane targeting and secretion of cofactor-containing proteins was described (Berks, 1996;Santini et al, 1998;Weiner et al, 1998). This system is Sec independent and uses a 'twin arginine' leader motif (Berks, 1996;Santini et al, 1998;Weiner et al, 1998).…”