Format

Send to

Choose Destination
See comment in PubMed Commons below
Biochemistry. 2007 Sep 4;46(35):10039-45. Epub 2007 Aug 14.

The effector domain of human Dlg tumor suppressor acts as a switch that relieves autoinhibition of kinesin-3 motor GAKIN/KIF13B.

Author information

1
Department of Pharmacology and UIC Cancer Center, University of Illinois College of Medicine, Chicago, Illinois 60612, USA.

Abstract

The activity of motor proteins must be tightly regulated in the cells to prevent unnecessary energy consumption and to maintain proper distribution of cellular components. Loading of the cargo molecule is one likely mechanism to activate an inactive motor. Here, we report that the activity of the kinesin-3 motor protein, GAKIN, is regulated by the direct binding of its protein cargo, human discs large (hDlg) tumor suppressor. Recombinant GAKIN exhibits potent microtubule gliding activity but has little microtubule-stimulated ATPase activity in solution, suggesting that it exists in an autoinhibitory form. In vitro binding measurements revealed that defined segments of GAKIN, particularly the MAGUK binding stalk (MBS) domain and the motor domain, mediate intramolecular interactions to confer globular protein conformation. Direct binding of the SH3-I3-GUK module of hDlg to the MBS domain of GAKIN activates the microtubule-stimulated ATPase activity of GAKIN by approximately 10-fold. We propose that the cargo-mediated regulation of motor activity constitutes a general paradigm for the activation of kinesins.

PMID:
17696365
PMCID:
PMC2525504
DOI:
10.1021/bi701169w
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Chemical Society Icon for PubMed Central
    Loading ...
    Support Center