2QRZ

Cdc42 bound to GMP-PCP: Induced Fit by Effector is Required

Summary for 2QRZ

• Entry DOI: 10.2210/pdb2qrz/pdb
• Descriptor: Cell division control protein 42 homolog precursor, MAGNESIUM ION, SULFATE ION, ... (5 entities in total)
• Functional Keywords: g-domain fold, g protein, gtpase, alternative splicing, gtp-binding, lipoprotein, membrane, methylation, nucleotide-binding, prenylation, cell cycle
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Lipid-anchor; Cytoplasmic side (Potential): P60953
• Total number of polymer chains: 2
• Total formula weight: 43301.62

Authors

Phillips, M.J.,Calero, G.,Chan, B.,Cerione, R.A. (deposition date: 2007-07-30, release date: 2008-03-18, Last modification date: 2024-11-20)

Primary citation

Phillips, M.J.,Calero, G.,Chan, B.,Ramachandran, S.,Cerione, R.A.
Effector Proteins Exert an Important Influence on the Signaling-active State of the Small GTPase Cdc42.
J.Biol.Chem., 283:14153-14164, 2008

PubMed Abstract: GTP-binding (G) proteins regulate the flow of information in cellular signaling pathways by alternating between a GTP-bound "active" state and a GDP-bound "inactive" state. Cdc42, a member of the Rho family of Ras-related small G-proteins, plays key roles in the regulation of cell shape, motility, and growth. Here we describe the high resolution x-ray crystal structure for Cdc42 bound to the GTP analog guanylyl beta,gamma-methylene-diphosphonate (GMP-PCP) (i.e. the presumed signaling-active state) and show that it is virtually identical to the structures for the signaling-inactive, GDP-bound form of the protein, contrary to what has been reported for Ras and other G-proteins. Especially surprising was that the GMP-PCP- and GDP-bound forms of Cdc42 did not show detectable differences in their Switch I and Switch II loops. Fluorescence studies using a Cdc42 mutant in which a tryptophan residue was introduced at position 32 of Switch I also showed that there was little difference in the Switch I conformation between the GDP- and GMP-PCP-bound states (i.e. <10%), which again differed from Ras where much larger changes in Trp-32 fluorescence were observed when comparing these two nucleotide-bound states (>30%). However, the binding of an effector protein induced significant changes in the Trp-32 emission specifically from GMP-PCP-bound Cdc42, as well as in the phosphate resonances for GTP bound to this G-protein as indicated in NMR studies. An examination of the available structures for Cdc42 complexed to different effector proteins, versus the x-ray crystal structure for GMP-PCP-bound Cdc42, provides a possible explanation for how effectors can distinguish between the GTP- and GDP-bound forms of this G-protein and ensure that the necessary conformational changes for signal propagation occur.

PubMed: 18348980
DOI: 10.1074/jbc.M706271200

Experimental method

X-RAY DIFFRACTION (2.4 Å)