InterPro domain: IPR036286

This entry represents a stuctural domain superfamily found in serine peptidases belonging to MEROPS peptidase families: S24 (LexA family, clan SF); S26A (signal peptidase I), S26B (signalase) and S26C TraF peptidase. This domain has a complex fold made of several coiled beta-sheets, which contains an SH3-like barrel structure.

The S26 family includes Escherichia coli signal peptidase, SPase, which is a membrane-bound endopeptidase with two N-terminal transmembrane segments and a C-terminal catalytic region [ 1 ]. SPase functions to release proteins that have been translocated into the inner membrane from the cell interior, by cleaving off their signal peptides. In SPase proteins, this domain is disrupted by the insertion of an additional all-beta subdomain.

• Note: This signature covers both the SH3-like barrel beta-ribbon domain and the all-beta subdomain inserted into it.

The S24 family includes:

• the lambda repressor CI/C2 family and related bacterial prophage repressor proteins [ 2 ].
• LexA, the repressor of genes in the cellular SOS response to DNA damage [ 3 ].
• MucA and the related UmuD proteins, which are lesion-bypass DNA polymerases, induced in response to mitogenic DNA damage [ 4 ]. UmuD is self-processed by its own serine protease activity during the SOS response.
• RulA, a component of the rulAB locus that confers resistance to UV.

All of these proteins, with the possible exception of RulA, interact with RecA, which activates self cleavage either derepressing transcription in the case of CI and LexA [ 5 ] or activating the lesion-bypass polymerase in the case of UmuD and MucA. UmuD'2, is the homodimeric component of DNA pol V, which is produced from UmuD by RecA-facilitated self-cleavage. The first 24 N-terminal residues of UmuD are removed; UmuD'2 is a DNA lesion bypass polymerase [ 6 , 6 ]. MucA [ 7 , 8 ], like UmuD, is a plasmid encoded a DNA polymerase (pol RI) which is converted into the active lesion-bypass polymerase by a self-cleavage reaction involving RecA [ 9 ].

This group of proteins also contains proteins not recognised as peptidases as well as those classified as non-peptidase homologues as they either have been found experimentally to be without peptidase activity, or lack amino acid residues that are believed to be essential for catalytic activity.

1. Crystal structure of a bacterial signal peptidase in complex with a beta-lactam inhibitor. Nature 396, 186-90
2. Crystal structure of the lambda repressor C-terminal domain provides a model for cooperative operator binding. Cell 101, 801-11
3. Crystal structure of LexA: a conformational switch for regulation of self-cleavage. Cell 106, 585-94
4. The UmuD' protein filament and its potential role in damage induced mutagenesis. Structure 4, 1401-12
5. Analysis of Escherichia coli RecA interactions with LexA, lambda CI, and UmuD by site-directed mutagenesis of recA. J. Bacteriol. 182, 1659-70
6. Converting a DNA damage checkpoint effector (UmuD2C) into a lesion bypass polymerase (UmuD'2C). EMBO J. 20, 4287-98
7. Intermolecular cleavage by UmuD-like enzymes: identification of residues required for cleavage and substrate specificity. J. Mol. Biol. 285, 2199-209
8. Plasmid-encoded MucB protein is a DNA polymerase (pol RI) specialized for lesion bypass in the presence of MucA', RecA, and SSB. Proc. Natl. Acad. Sci. U.S.A. 97, 11227-31
9. Genetic and biochemical characterization of a novel umuD mutation: insights into a mechanism for UmuD self-cleavage. J. Bacteriol. 183, 347-57