Mechanism, specificity, and physiology of signal peptide peptidase (SPP) and SPP-like proteases

Research output: Contribution to journalReview articleContributedpeer-review

Contributors

  • Matthias Voss - , Ludwig Maximilian University of Munich (Author)
  • Bernd Schröder - , Institute of Physiological Chemistry, Kiel University (Author)
  • Regina Fluhrer - , Ludwig Maximilian University of Munich, German Center for Neurodegenerative Diseases (DZNE) (Author)

Abstract

Signal peptide peptidase (SPP) and the homologous SPP-like (SPPL) proteases SPPL2a, SPPL2b, SPPL2c and SPPL3 belong to the family of GxGD intramembrane proteases. SPP/SPPLs selectively cleave transmembrane domains in type II orientation and do not require additional co-factors for proteolytic activity. Orthologues of SPP and SPPLs have been identified in other vertebrates, plants, and eukaryotes. In line with their diverse subcellular localisations ranging from the ER (SPP, SPPL2c), the Golgi (SPPL3), the plasma membrane (SPPL2b) to lysosomes/late endosomes (SPPL2a), the different members of the SPP/SPPL family seem to exhibit distinct functions. Here, we review the substrates of these proteases identified to date as well as the current state of knowledge about the physiological implications of these proteolytic events as deduced from in vivo studies. Furthermore, the present knowledge on the structure of intramembrane proteases of the SPP/SPPL family, their cleavage mechanism and their substrate requirements are summarised. This article is part of a Special Issue entitled: Intramembrane Proteases.

Details

Original languageEnglish
Pages (from-to)2828-2839
Number of pages12
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1828
Issue number12
Publication statusPublished - 2013
Peer-reviewedYes

External IDs

PubMed 24099004

Keywords

ASJC Scopus subject areas

Keywords

  • GxGD proteases, Intramembrane-cleaving proteases, Regulated intramembrane proteolysis, Signal peptide peptidase, Signal peptide peptidase-like