A tale of two GTPases in cotranslational protein targeting

Authors

  • Ishu Saraogi,

    1. Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125
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  • David Akopian,

    1. Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125
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  • Shu-Ou Shan

    Corresponding author
    1. Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125
    • Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E. California Blvd, Pasadena, CA 91125
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  • Dr. Shan is the 2011 recipient of the Protein Society Irving Signal Young Investigator Award recognizing a significant contribution to the study of proteins by a scientist who is in the early stages of an independent career.

Abstract

Guanosine triphosphatases (GTPases) comprise a superfamily of proteins that provide molecular switches to regulate numerous cellular processes. The “GTPase switch” paradigm, in which a GTPase acts as a bimodal switch that is turned “on” and “off” by external regulatory factors, has been used to interpret the regulatory mechanism of many GTPases. Recent work on a pair of GTPases in the signal recognition particle (SRP) pathway has revealed a distinct mode of GTPase regulation. Instead of the classical GTPase switch, the two GTPases in the SRP and SRP receptor undergo a series of conformational changes during their dimerization and reciprocal activation. Each conformational rearrangement provides a point at which these GTPases can communicate with and respond to their upstream and downstream biological cues, thus ensuring the spatial and temporal precision of all the molecular events in the SRP pathway. We suggest that the SRP and SRP receptor represent an emerging class of “multistate” regulatory GTPases uniquely suited to provide exquisite control over complex cellular pathways that require multiple molecular events to occur in a highly coordinated fashion.

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