CYSTM, a novel cysteine-rich transmembrane module with a role in stress tolerance across eukaryotes

Abstract

Using sensitive sequence profile analysis, we identify a hitherto uncharacterized cysteine-rich, transmembrane (TM) module, CYSTM, found in a wide range of tail-anchored membrane proteins across eukaryotes. This superfamily includes Schizosaccharomyces Uvi15, Arabidopsis PCC1, Digtaria CDT1 and Saccharomyces proteins YDL012C and YDR210W, which have all been implicated in resistance/response to stress or pathogens. Based on the pattern of conserved cysteines and data from different chemical genetics studies, we suggest that CYSTM proteins might have critical role in responding to deleterious compounds at the plasma membrane via chelation or redox-based mechanisms. Thus, CYSTM proteins are likely to be part of a novel cellular protective mechanism that is widely active in eukaryotes, including humans.

Supplementary information: Supplementary data are available at Bioinformatics online.

Fig. 1.

Multiple sequence alignment of the CYSTM domain superfamily. The columns were colored according to the consensus shown below the alignment, and the predicted secondary structure is shown on top. The sequences are labeled using the gene name, species abbreviation and GenBank gi number and sequence identifiers. The species abbreviations are—Abis: Agaricus bisporus; Atha: Arabidopsis thaliana; Agos: Ashbya gossypii; Anid: Aspergillus nidulans; Aory: Aspergillus oryzae; Btau: Bos taurus; Bfuc: Botryotinia fuckeliana; Cbri: Caenorhabditis briggsae; Cele: Caenorhabditis elegans; Calb: Candida albicans; Cdub: Candida dubliniensis; Cgla: Candida glabrata; Crei: Chlamydomonas reinhardtii; Cint: Ciona intestinalis; Drer: Danio rerio; Dcil: D.ciliaris; Dgri: Drosophila grimshawi; Gzea: Gibberella zeae; Hsap: Homo sapiens; Hmag: Hydra magnipapillata; Klac: Kluyveromyces lactis; Lbic: Laccaria bicolor; Mdom: Monodelphis domestica; Mbre: Monosiga brevicollis MX1; Mmus: Mus musculus; Nfis: Neosartorya fischeri; Osat: O.sativa; Ptro: Pan troglodytes; Pchr: Penicillium chrysogenum; Pmar: Penicillium marneffei; Pmar: Perkinsus marinus; Ppat: Physcomitrella patens; Psit: Picea sitchensis; Pans: Podospora anserina; Rnor: Rattus norvegicus; Rcom: Ricinus communis; Scer: S.cerevisiae; Sjap: Schizosaccharomyces japonicus; Spom: S.pombe; Sscl: Sclerotinia sclerotiorum; Ssta: Sporobolus stapfianus; Spur: Strongylocentrotus purpuratus; Tgut: Taeniopygia guttata; Xtro: Xenopus tropicalis; Xlae: Xenopus laevis; Ylip: Yarrowia lipolytica; Zmay: Zea mays.

Fig. 2.

A speculative model of the CYSTM module-anchored plasma in the membrane. Lipids are represented with black tail and yellow head groups. The protein transmembrane regions colored in red, with cysteines are represented as brown dashes. The intracellular unstructured regions are shown as random coil. The conserved acidic position (usually Asp) is shown binding the extracellular lipid head.