6VIH

The ligand-free structure of mouse RABL3

Summary for 6VIH

• Entry DOI: 10.2210/pdb6vih/pdb
• Descriptor: Rab-like protein 3 (1 entity in total)
• Functional Keywords: immune system, gtpase
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 2
• Total formula weight: 55453.92

Authors

Su, L.,Tomchick, D.R.,Beutler, B. (deposition date: 2020-01-13, release date: 2020-04-08, Last modification date: 2024-03-06)

Primary citation

Zhong, X.,Su, L.,Yang, Y.,Nair-Gill, E.,Tang, M.,Anderton, P.,Li, X.,Wang, J.,Zhan, X.,Tomchick, D.R.,Brautigam, C.A.,Moresco, E.M.Y.,Choi, J.H.,Beutler, B.
Genetic and structural studies of RABL3 reveal an essential role in lymphoid development and function.
Proc.Natl.Acad.Sci.USA, 117:8563-8572, 2020

PubMed Abstract: The small GTPase RABL3 is an oncogene of unknown physiological function. Homozygous knockout alleles of mouse were embryonic lethal, but a viable hypomorphic allele ( []) 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 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 displayed a large compensatory alteration in switch I, which adopted a β-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 phenotype. One such effector may be GPR89, putatively an ion channel or G protein-coupled receptor (GPCR). RABL3, but not RABL3, strongly associated with and stabilized GPR89, and an -ethyl--nitrosourea (ENU)-induced mutation () in phenocopied .

PubMed: 32220963
DOI: 10.1073/pnas.2000703117

Experimental method

X-RAY DIFFRACTION (2.993 Å)