title: Crystal structure of a Chlamydomonas reinhardtii flagellar RabGAP TBC-domain at 1.8 Å resolution.
abstract: Rab GTPases play a crucial role in the regulation of many intracellular membrane trafficking pathways including endocytosis and ciliogenesis. Rab GTPase activating proteins (RabGAPs) increase the GTP hydrolysis rate of Rab GTPases and turn them into guanine nucleotide diphosphate (GDP) bound inactive form. Here, we determined the crystal structure of the putative catalytic domain of a RabGAP (which we name CrfRabGAP) that is found in the flagellar proteome of the unicellular green alga Chlamydomonas reinhardtii. BLAST searches revealed potential human orthologues of CrfRabGAP as TBC1D3 and TBC1D26. Sequence and structural comparison with other canonical RabGAPs revealed that the CrfRabGAP does not contain the canonical catalytic residues required for the activation of Rab GTPases. The function of noncanonical RabGAPs-like CrfRabGAP might be to serve as Rab effectors rather than activators.
authors.affiliation: Department of Structural Cell Biology, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, D-82152, Martinsried, Germany.
authors.forename: Sagar
authors.initials: S
authors.lastname: Bhogaraju
authors.forename: Esben
authors.initials: E
authors.lastname: Lorentzen
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D016825:Chlamydomonas reinhardtii / Q000378:metabolism*; D018360:Crystallography, X-Ray; D005407:Flagella / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000648:ultrastructure*; D008969:Molecular Sequence Data; D020691:rab GTP-Binding Proteins / Q000378:metabolism
chemical_list: D020690:GTPase-Activating Proteins; D020691:rab GTP-Binding Proteins
keywords: GTPase; RabGAP; Tre2-Bub2-Cdc16 domain; cilium; flagellum; intraflagellar transport