CPDadh: A new peptidase family homologous to the cysteine protease domain in bacterial MARTX toxins

Authors

  • Jimin Pei,

    Corresponding author
    1. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9050
    • Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, Texas 75390-9050
    Search for more papers by this author
  • Patrick J. Lupardus,

    1. Department of Molecular and Cellular Physiology and Department of Structural Biology, Stanford University School of Medicine, Stanford, California 94305
    Search for more papers by this author
  • K. Christopher Garcia,

    1. Department of Molecular and Cellular Physiology and Department of Structural Biology, Stanford University School of Medicine, Stanford, California 94305
    2. Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305
    Search for more papers by this author
  • Nick V. Grishin

    1. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9050
    2. Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9050
    Search for more papers by this author

Abstract

A cysteine protease domain (CPD) has been recently discovered in a group of multifunctional, autoprocessing RTX toxins (MARTX) and Clostridium difficile toxins A and B. These CPDs (referred to as CPDmartx) autocleave the toxins to release domains with toxic effects inside host cells. We report identification and computational analysis of CPDadh, a new cysteine peptidase family homologous to CPDmartx. CPDadh and CPDmartx share a Rossmann-like structural core and conserved catalytic residues. In bacteria, domains of the CPDadh family are present at the N-termini of a diverse group of putative cell-cell interaction proteins and at the C-termini of some RHS (recombination hot spot) proteins. In eukaryotes, catalytically inactive members of the CPDadh family are found in cell surface protein NELF (nasal embryonic LHRH factor) and some putative signaling proteins.

Ancillary