6AXG

Structure of RasGRP4 in complex with HRas

Summary for 6AXG

• Entry DOI: 10.2210/pdb6axg/pdb
• Descriptor: RAS guanyl-releasing protein 4, GTPase HRas (2 entities in total)
• Functional Keywords: signaling protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm: Q8TDF6; Cell membrane. Isoform 2: Nucleus: P01112
• Total number of polymer chains: 12
• Total formula weight: 395195.29

Authors

Kondo, Y.,Iwig, J.S.,Kuriyan, J. (deposition date: 2017-09-06, release date: 2017-10-11, Last modification date: 2023-10-04)

Primary citation

Vercoulen, Y.,Kondo, Y.,Iwig, J.S.,Janssen, A.,White, K.A.,Amini, M.,Barber, D.L.,Kuriyan, J.,Roose, J.P.
A histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1.
Elife, 6:-, 2017

PubMed Abstract: RasGRPs are guanine nucleotide exchange factors that are specific for Ras or Rap, and are important regulators of cellular signaling. Aberrant expression or mutation of RasGRPs results in disease. An analysis of RasGRP1 SNP variants led to the conclusion that the charge of His 212 in RasGRP1 alters signaling activity and plasma membrane recruitment, indicating that His 212 is a pH sensor that alters the balance between the inactive and active forms of RasGRP1. To understand the structural basis for this effect we compared the structure of autoinhibited RasGRP1, determined previously, to those of active RasGRP4:H-Ras and RasGRP2:Rap1b complexes. The transition from the autoinhibited to the active form of RasGRP1 involves the rearrangement of an inter-domain linker that displaces inhibitory inter-domain interactions. His 212 is located at the fulcrum of these conformational changes, and structural features in its vicinity are consistent with its function as a pH-dependent switch.

PubMed: 28952923
DOI: 10.7554/eLife.29002

Experimental method

X-RAY DIFFRACTION (3.302 Å)