6vik | pdb_00006vik

Crystal structure of mouse xm RABL3 in complex with GTPgammsS

spinqualitylabelsall models 6vik, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6vik is a 1 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GSP, MG Gene: Rabl3 (LK3 transgenic mice) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The small GTPase RABL3 is an oncogene of unknown physiological function. Homozygous knockout alleles of mouse Rabl3 were embryonic lethal, but a viable hypomorphic allele (xiamen [xm]) causing in-frame deletion of four amino acids from the interswitch region resulted in profound defects in lymphopoiesis. Impaired lymphoid progenitor development led to deficiencies of B cells, T cells, and natural killer (NK) cells in Rabl3 (xm/xm) mice. T cells and NK cells exhibited impaired cytolytic activity, and mice infected with mouse cytomegalovirus (MCMV) displayed elevated titers in the spleen. Myeloid cells were normal in number and function. Biophysical and crystallographic studies demonstrated that RABL3 formed a homodimer in solution via interactions between the effector binding surfaces on each subunit; monomers adopted a typical small G protein fold. RABL3(xm) displayed a large compensatory alteration in switch I, which adopted a beta-strand configuration normally provided by the deleted interswitch residues, thereby permitting homodimer formation. Dysregulated effector binding due to conformational changes in the switch I-interswitch-switch II module likely underlies the xm phenotype. One such effector may be GPR89, putatively an ion channel or G protein-coupled receptor (GPCR). RABL3, but not RABL3(xm), strongly associated with and stabilized GPR89, and an N-ethyl-N-nitrosourea (ENU)-induced mutation (explorer) in Gpr89 phenocopied Rabl3 (xm). Genetic and structural studies of RABL3 reveal an essential role in lymphoid development and function.,Zhong X, Su L, Yang Y, Nair-Gill E, Tang M, Anderton P, Li X, Wang J, Zhan X, Tomchick DR, Brautigam CA, Moresco EMY, Choi JH, Beutler B Proc Natl Acad Sci U S A. 2020 Mar 27. pii: 2000703117. doi:, 10.1073/pnas.2000703117. PMID:32220963 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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