2dpx
Crystal Structure of human Rad GTPase
Structural highlights
FunctionRAD_HUMAN May play an important role in cardiac antiarrhythmia via the strong suppression of voltage-gated L-type Ca(2+) currents. Regulates voltage-dependent L-type calcium channel subunit alpha-1C trafficking to the cell membrane (By similarity). Inhibits cardiac hypertrophy through the calmodulin-dependent kinase II (CaMKII) pathway. Inhibits phosphorylation and activation of CAMK2D.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedRad (Ras associated with diabetes) is an RGK-family small GTPase that is over-expressed in the skeletal muscle of humans with type II diabetes. Unlike other small GTPases, RGK family members including Rad lack several conserved residues in the GTPase domain. Here, we report the crystal structure of the GTPase domain of human Rad in the GDP-bound form at 1.8 A resolution. The structure revealed unexpected disordered structures of both switches I and II. We showed that the conformational flexibility of both switches is caused by non-conservative substitutions in the G2 and G3 motifs forming the switch cores together with other substitutions in the structural elements interacting with the switches. Glycine-rich sequences of the switches would also contribute to the flexibility. Switch I lacks the conserved phenylalanine that makes non-polar interactions with the guanine base in H-Ras. Instead, water-mediated hydrogen bonding interactions were observed in Rad. The GDP molecule is located at the same position as in H-Ras and adopts a similar conformation as that bound in H-Ras. This similarity seems to be endowed by the conserved hydrogen bonding interactions with the guanine base-recognition loops and the magnesium ion that has a typical octahedral coordination shell identical to that in H-Ras. Crystal structure of human Rad GTPase of the RGK-family.,Yanuar A, Sakurai S, Kitano K, Hakoshima T Genes Cells. 2006 Aug;11(8):961-8. PMID:16866878[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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