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A "push and slide" mechanism allows sequence-insensitive translocation of secretory proteins by the SecA ATPase.

ABSTRACT: In bacteria, most secretory proteins are translocated across the plasma membrane by the interplay of the SecA ATPase and the SecY channel. How SecA moves a broad range of polypeptide substrates is only poorly understood. Here we show that SecA moves polypeptides through the SecY channel by a "push and slide" mechanism. In its ATP-bound state, SecA interacts through a two-helix finger with a subset of amino acids in a substrate, pushing them into the channel. A polypeptide can also passively slide back and forth when SecA is in the predominant ADP-bound state or when SecA encounters a poorly interacting amino acid in its ATP-bound state. SecA performs multiple rounds of ATP hydrolysis before dissociating from SecY. The proposed push and slide mechanism is supported by a mathematical model and explains how SecA allows translocation of a wide range of polypeptides. This mechanism may also apply to hexameric polypeptide-translocating ATPases.

SUBMITTER: Bauer BW

PROVIDER: S-EPMC4104599 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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A "push and slide" mechanism allows sequence-insensitive translocation of secretory proteins by the SecA ATPase.

Bauer Benedikt W BW Shemesh Tom T Chen Yu Y Rapoport Tom A TA

Cell 20140601 6

In bacteria, most secretory proteins are translocated across the plasma membrane by the interplay of the SecA ATPase and the SecY channel. How SecA moves a broad range of polypeptide substrates is only poorly understood. Here we show that SecA moves polypeptides through the SecY channel by a "push and slide" mechanism. In its ATP-bound state, SecA interacts through a two-helix finger with a subset of amino acids in a substrate, pushing them into the channel. A polypeptide can also passively slid ...[more]

PMID: 24906156

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