Help Privacy Policy Disclaimer
  Advanced SearchBrowse




Journal Article

Alternative splicing of Rac1 generates Rac1b, a self-activating GTPase.


Blumenstein,  Lars
Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society;

Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available

Fiegen, D., Haeusler, L., Blumenstein, L., Herbrand, U., Dvorsky, R., Vetter, I. R., et al. (2004). Alternative splicing of Rac1 generates Rac1b, a self-activating GTPase. The Journal of Biological Chemistry, 279(6), 4743-4749. doi:10.1074/jbc.M310281200.

Cite as: https://hdl.handle.net/21.11116/0000-0001-EE27-8
Rac1b was recently identified in malignant colorectal tumors as an alternative splice variant of Rac1 containing a 19-amino acid insertion next to the switch II region. The structures of Rac1b in the GDP- and the GppNHp-bound forms, determined at a resolution of 1.75 A, reveal that the insertion induces an open switch I conformation and a highly mobile switch II. As a consequence, Rac1b has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins. Interestingly, Rac1b is able to bind the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner, suggesting that the insertion does not completely abolish effector interaction. The presented study provides insights into the structural and biochemical mechanism of a self-activating GTPase.