Publication

Preprotein Conformational Dynamics Drive Bivalent Translocase Docking and Secretion

Sardis, M. F., Tsirigotaki, A., Chatzi, K. E., Portaliou, A. G., Gouridis, G., Karamanou, S. & Economou, A., 5-Jul-2017, In : Structure. 25, 7, p. 1056-+ 18 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Marios Frantzeskos Sardis
  • Alexandra Tsirigotaki
  • Katerina Elias Chatzi
  • Athina George Portaliou
  • Giorgos Gouridis
  • Spyridoula Karamanou
  • Anastassios Economou

Most bacterial secretory proteins destined beyond the plasma membrane are secreted post-translationally by the Sec translocase. In the first step of translocation, preproteins are targeted for binding to their 2-site receptor SecA, the peripheral ATPase subunit of the translocase. We now reveal that secretory preproteins use a dual-key mechanism to bridge the signal peptide and mature domain receptor sites and cooperatively enhance their affinities. Docking of targeting-competent mature domains requires that their extensive disorder is finely tuned. This is achieved through amino-terminal mature domain regions acting as conformational rheostats. By being linked to the rheostats, signal peptides regulate long-range preprotein disorder. Concomitant conformational changes in SecA sterically adapt its two receptor sites to optimally recognize hundreds of dissimilar preproteins. This novel intramolecular conformational crosstalk in the preprotein chains and the dynamic interaction with their receptor are mechanistically coupled to preprotein engagement in the translocase and essential for secretion.

Original languageEnglish
Pages (from-to)1056-+
Number of pages18
JournalStructure
Volume25
Issue number7
Publication statusPublished - 5-Jul-2017
Externally publishedYes

    Keywords

  • ESCHERICHIA-COLI, PROTEIN-TRANSLOCATION, ALKALINE-PHOSPHATASE, UNSTRUCTURED REGIONS, MEMBRANE INSERTION, MASS-SPECTROMETRY, STRUCTURAL BASIS, SECA ATPASE, SEQUENCE, MOTOR

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