TY  - JOUR
AU  - Krishnamurthy, Srinath
AU  - Sardis, Marios-Frantzeskos
AU  - Eleftheriadis, Nikolaos
AU  - Chatzi, Katerina E.
AU  - Smit, Jochem H.
AU  - Karathanou, Konstantina
AU  - Gouridis, Giorgos
AU  - Portaliou, Athina G.
AU  - Bondar, Ana-Nicoleta
AU  - Karamanou, Spyridoula
AU  - Economou, Anastassios
TI  - Preproteins couple the intrinsic dynamics of SecA to its ATPase cycle to translocate via a catch and release mechanism
JO  - Cell reports
VL  - 38
IS  - 6
SN  - 2211-1247
CY  - [New York, NY]
PB  - Elsevier
M1  - FZJ-2023-00943
SP  - 110346 -
PY  - 2022
AB  - Protein machines undergo conformational motions to interact with and manipulate polymeric substrates. The Sec translocase promiscuously recognizes, becomes activated, and secretes >500 non-folded preprotein clients across bacterial cytoplasmic membranes. Here, we reveal that the intrinsic dynamics of the translocase ATPase, SecA, and of preproteins combine to achieve translocation. SecA possesses an intrinsically dynamic preprotein clamp attached to an equally dynamic ATPase motor. Alternating motor conformations are finely controlled by the γ-phosphate of ATP, while ADP causes motor stalling, independently of clamp motions. Functional preproteins physically bridge these independent dynamics. Their signal peptides promote clamp closing; their mature domain overcomes the rate-limiting ADP release. While repeated ATP cycles shift the motor between unique states, multiple conformationally frustrated prongs in the clamp repeatedly “catch and release” trapped preprotein segments until translocation completion. This universal mechanism allows any preprotein to promiscuously recognize the translocase, usurp its intrinsic dynamics, and become secreted.
LB  - PUB:(DE-HGF)16
C6  - 35139375
UR  - <Go to ISI:>//WOS:000754407500004
DO  - DOI:10.1016/j.celrep.2022.110346
UR  - https://juser.fz-juelich.de/record/943337
ER  -