1RYH

Alternative Splicing of Rac1 Generates Rac1b, a Self-activating GTPase

Summary for 1RYH

• Entry DOI: 10.2210/pdb1ryh/pdb
• Related: 1RYF
• Descriptor: ras-related C3 botulinum toxin substrate 1 isoform Rac1b, MAGNESIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, ... (4 entities in total)
• Functional Keywords: gtp binding, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Lipid-anchor; Cytoplasmic side (By similarity): P63000
• Total number of polymer chains: 2
• Total formula weight: 45832.60

Authors

Ahmadian, M.R.,Fiegen, D. (deposition date: 2003-12-22, release date: 2004-01-27, Last modification date: 2023-10-25)

Primary citation

Fiegen, D.,Haeusler, L.C.,Blumenstein, L.,Herbrand, U.,Dvorsky, R.,Vetter, I.R.,Ahmadian, M.R.
Alternative Splicing of Rac1 Generates Rac1b, a Self-activating GTPase
J.Biol.Chem., 279:4743-4749, 2004

PubMed Abstract: 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.

PubMed: 14625275
DOI: 10.1074/jbc.M310281200

Experimental method

X-RAY DIFFRACTION (1.75 Å)