4M9Q

Crystal structure of C-terminally truncated Arl13B from Chlamydomonas rheinhardtii bound to GppNHp

Summary for 4M9Q

• Entry DOI: 10.2210/pdb4m9q/pdb
• Descriptor: ARF-like GTPase, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: gtpase, g domain, joubert syndrome, cilia, hydrolase
• Biological source: Chlamydomonas reinhardtii
• Cellular location: Cell projection, cilium membrane (By similarity): A8INQ0
• Total number of polymer chains: 3
• Total formula weight: 79484.63

Authors

Miertzschke, M.,Koerner, C.,Spoerner, M.,Wittinghofer, A. (deposition date: 2013-08-15, release date: 2013-11-06, Last modification date: 2023-09-20)

Primary citation

Miertzschke, M.,Koerner, C.,Spoerner, M.,Wittinghofer, A.
Structural insights into the small G-protein Arl13B and implications for Joubert syndrome.
Biochem.J., 457:301-311, 2014

PubMed Abstract: Ciliopathies are human diseases arising from defects in primary or motile cilia. The small G-protein Arl13B (ADP-ribosylation factor-like 13B) localizes to microtubule doublets of the ciliary axoneme and is mutated in Joubert syndrome. Its GDP/GTP mechanistic cycle and the effect of its mutations in patients with Joubert syndrome remain elusive. In the present study we applied high resolution structural and biochemical approaches to study Arl13B. The crystal structure of Chlamydomonas rheinhardtii Arl13B, comprising the G-domain and part of its unique C-terminus, revealed an incomplete active site, and together with biochemical data the present study accounts for the absence of intrinsic GTP hydrolysis by this protein. The structure shows that the residues representing patient mutations R79Q and R200C are involved in stabilizing important intramolecular interactions. Our studies suggest that Arg79 is crucial for the GDP/GTP conformational change by stabilizing the large two-residue register shift typical for Arf (ADP-ribosylation factor) and Arl subfamily proteins. A corresponding mutation in Arl3 induces considerable defects in effector and GAP (GTPase-activating protein) binding, suggesting a loss of Arl13B function in patients with Joubert syndrome.

PubMed: 24168557
DOI: 10.1042/BJ20131097

Experimental method

X-RAY DIFFRACTION (2.5 Å)