title: Structural basis of Rab5-Rabaptin5 interaction in endocytosis.
abstract: Rab5 is a small GTPase that regulates early endosome fusion. We present here the crystal structure of the Rab5 GTPase domain in complex with a GTP analog and the C-terminal domain of effector Rabaptin5. The proteins form a dyad-symmetric Rab5-Rabaptin5(2)-Rab5 ternary complex with a parallel coiled-coil Rabaptin5 homodimer in the middle. Two Rab5 molecules bind independently to the Rabaptin5 dimer using their switch and interswitch regions. The binding does not involve the Rab complementarity-determining regions. We also present the crystal structures of two distinct forms of GDP-Rab5 complexes, both of which are incompatible with Rabaptin5 binding. One has a dislocated and disordered switch I but a virtually intact switch II, whereas the other has its beta-sheet and both switch regions reorganized. Biochemical and functional analyses show that the crystallographically observed Rab5-Rabaptin5 complex also exists in solution, and disruption of this complex by mutation abrogates endosome fusion.
authors.affiliation: Crystallography Research Program, Oklahoma Medical Research Foundation, 825 N.E. 13th Street, Oklahoma City, Oklahoma 73104, USA.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhu
authors.forename: Peng
authors.initials: P
authors.lastname: Zhai
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Simon
authors.initials: S
authors.lastname: Terzyan
authors.forename: Guangpu
authors.initials: G
authors.lastname: Li
authors.forename: Xuejun C
authors.initials: XC
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D004705:Endocytosis; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D020696:rab5 GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins