Structure-function analysis of PrsA reveals roles for the parvulin-like and flanking N- and C-terminal domains in protein folding and secretion in Bacillus subtilis

Marika Vitikainen, Ilkka Lappalainen, Raili Seppala, Haike Antelmann, Harry Boer, Suvi Taira, Harri Savilahti, Michael Hecker, Mauno Vihinen, Matti Sarvas, Vesa P. Kontinen (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

81 Citations (Scopus)

Abstract

The PrsA protein of Bacillus subtilis is an essential membrane-bound lipoprotein that is assumed to assist post-translocational folding of exported proteins and stabilize them in the compartment between the cytoplasmic membrane and cell wall. This folding activity is consistent with the homology of a segment of PrsA with parvulin-type peptidyl-prolyl cis/trans isomerases (PPIase). In this study, molecular modeling showed that the parvulin-like region can adopt a parvulin-type fold with structurally conserved active site residues. PrsA exhibits PPIase activity in a manner dependent on the parvulin-like domain. We constructed deletion, peptide insertion, and amino acid substitution mutations and demonstrated that the parvulin-like domain as well as flanking N- and C-terminal domains are essential for in vivo PrsA function in protein secretion and growth. Surprisingly, none of the predicted active site residues of the parvulin-like domain was essential for growth and protein secretion, although several active site mutations reduced or abolished the PPIase activity or the ability of PrsA to catalyze proline-limited protein folding in vitro. Our results indicate that PrsA is a PPIase, but the essential role in vivo seems to depend on some non-PPIase activity of both the parvulin-like and flanking domains.
Original languageEnglish
Pages (from-to)19302 - 19314
Number of pages13
JournalJournal of Biological Chemistry
Volume279
Issue number18
DOIs
Publication statusPublished - 2004
MoE publication typeA1 Journal article-refereed

Keywords

  • protein secretion
  • proteins
  • Bacillus subtilis

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