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Publication Abstract from PubMed

Ciliopathies are human diseases arising from defects in primary or motile cilia. The small G protein Arl13B localizes to microtubule doublets of the ciliary axoneme and is mutated in Joubert Syndrome. Its GDP-GTP mechanistic cycle and the impact of patient mutations remain elusive. Here, we applied high resolution structural and biochemical approaches to study Arl13B. The crystal structure of Chlamydomonas rheinhardtii Arl13B comprising Gdomain and part of its unique C-terminus and biochemical experiments reveal the lack of intrinsic hydrolysis and the absence of a catalytic residue in the active site. The structure shows residues representing patient mutations R79Q and R200C to be involved in stabilizing important intramolecular interactions. Our studies suggest that Arg79 is crucial for the GDPGTP conformational change by stabilizing the large two residue register shift typical for Arf and Arl subfamily proteins. A corresponding mutation in Arl3 induces considerable defects in effector and GAP binding suggesting a loss of Arl13B function in Joubert Syndrome patients.

Structural insights into the small G protein Arl13B and implications for Joubert syndrome.,Miertzschke M, Koerner C, Spoerner M, Wittinghofer A Biochem J. 2013 Oct 30. PMID:24168557^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.