1I4D

CRYSTAL STRUCTURE ANALYSIS OF RAC1-GDP COMPLEXED WITH ARFAPTIN (P21)

Summary for 1I4D

• Entry DOI: 10.2210/pdb1i4d/pdb
• Related: 1I49 1I4L
• NMR Information: BMRB: 5511
• Descriptor: ARFAPTIN 2, RAS-RELATED C3 BOTULINUM TOXIN SUBSTRATE 1, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: coiled coil, g-protein, complex, signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane ; Lipid-anchor ; Cytoplasmic side : P63000
• Total number of polymer chains: 3
• Total formula weight: 73173.73

Authors

Tarricone, C.,Xiao, B.,Justin, N.,Gamblin, S.J.,Smerdon, S.J. (deposition date: 2001-02-20, release date: 2001-05-16, Last modification date: 2024-02-07)

Primary citation

Tarricone, C.,Xiao, B.,Justin, N.,Walker, P.A.,Rittinger, K.,Gamblin, S.J.,Smerdon, S.J.
The structural basis of Arfaptin-mediated cross-talk between Rac and Arf signalling pathways.
Nature, 411:215-219, 2001

PubMed Abstract: Small G proteins are GTP-dependent molecular switches that regulate numerous cellular functions. They can be classified into homologous subfamilies that are broadly associated with specific biological processes. Cross-talk between small G-protein families has an important role in signalling, but the mechanism by which it occurs is poorly understood. The coordinated action of Arf and Rho family GTPases is required to regulate many cellular processes including lipid signalling, cell motility and Golgi function. Arfaptin is a ubiquitously expressed protein implicated in mediating cross-talk between Rac (a member of the Rho family) and Arf small GTPases. Here we show that Arfaptin binds specifically to GTP-bound Arf1 and Arf6, but binds to Rac.GTP and Rac.GDP with similar affinities. The X-ray structure of Arfaptin reveals an elongated, crescent-shaped dimer of three-helix coiled-coils. Structures of Arfaptin with Rac bound to either GDP or the slowly hydrolysable analogue GMPPNP show that the switch regions adopt similar conformations in both complexes. Our data highlight fundamental differences between the molecular mechanisms of Rho and Ras family signalling, and suggest a model of Arfaptin-mediated synergy between the Arf and Rho family signalling pathways.

PubMed: 11346801
DOI: 10.1038/35075620

Experimental method

X-RAY DIFFRACTION (2.5 Å)