6axg
From Proteopedia
Structure of RasGRP4 in complex with HRas
Structural highlights
FunctionGRP4_HUMAN Functions as a cation- and diacylglycerol (DAG)-regulated nucleotide exchange factor activating Ras through the exchange of bound GDP for GTP. May function in mast cells differentiation.[1] [2] [3] [4] Publication Abstract from PubMedRasGRPs 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 that 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. A histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1.,Vercoulen Y, Kondo Y, Iwig JS, Janssen A, White KA, Amini M, Barber DL, Kuriyan J, Roose JP Elife. 2017 Sep 27;6. pii: e29002. doi: 10.7554/eLife.29002. PMID:28952923[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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