3QXL

Crystal structure of the CDC25 Domain from Ral-specific Guanine-nucleotide Exchange Factor RalGPS1a

Summary for 3QXL

• Entry DOI: 10.2210/pdb3qxl/pdb
• Descriptor: Ras-specific guanine nucleotide-releasing factor RalGPS1 (2 entities in total)
• Functional Keywords: cdc25 domain homology, guanine-nucleotide exchange factor, small gtpase ral subfamily, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm (By similarity): Q5JS13
• Total number of polymer chains: 2
• Total formula weight: 62301.82

Authors

Peng, W.,Xu, J.,Guan, X.,Sun, Y.,Li, X.,Zhang, X.C.,Rao, Z. (deposition date: 2011-03-02, release date: 2011-05-11, Last modification date: 2024-02-21)

Primary citation

Peng, W.,Xu, J.,Guan, X.,Sun, Y.,Zhang, X.C.,Li, X.,Rao, Z.
Structural study of the Cdc25 domain from Ral-specific guanine-nucleotide exchange factor RalGPS1a.
Protein Cell, 2:308-319, 2011

PubMed Abstract: The guanine-nucleotide exchange factor (GEF) RalGPS1a activates small GTPase Ral proteins such as RalA and RalB by stimulating the exchange of Ral bound GDP to GTP, thus regulating various downstream cellular processes. RalGPS1a is composed of an Nterminal Cdc25-like catalytic domain, followed by a PXXP motif and a C-terminal pleckstrin homology (PH) domain. The Cdc25 domain of RalGPS1a, which shares about 30% sequence identity with other Cdc25-domain proteins, is thought to be directly engaged in binding and activating the substrate Ral protein. Here we report the crystal structure of the Cdc25 domain of RalGPS1a. The bowl shaped structure is homologous to the Cdc25 domains of SOS and RasGRF1. The most remarkable difference between these three Cdc25 domains lies in their active sites, referred to as the helical hairpin region. Consistent with previous enzymological studies, the helical hairpin of RalGPS1a adopts a conformation favorable for substrate binding. A modeled RalGPS1a-RalA complex structure reveals an extensive binding surface similar to that of the SOS-Ras complex. However, analysis of the electrostatic surface potential suggests an interaction mode between the RalGPS1a active site helical hairpin and the switch 1 region of substrate RalA distinct from that of the SOS-Ras complex.

PubMed: 21494904
DOI: 10.1007/s13238-011-1036-z

Experimental method

X-RAY DIFFRACTION (2.237 Å)