Structure of the small GTPase Rab27b shows an unexpected swapped dimer.
Members of the Rab family of small GTPases regulate membrane traffic within the cell by recruiting their specific effectors in a nucleotide-dependent manner. The Rab27 subfamily consists of Rab27a and Rab27b, which share 70% sequence identity. By interacting with a large set of effector proteins such as melanophilin and granuphilin, both Rab27a and Rab27b regulate the exocytosis of secretory lysosomes. Here, the crystal structures of mouse Rab27b in complex with GDP have been determined in three distinct crystal lattices. Surprisingly, Rab27b-GDP exists in an open conformation with protruding switch and interswitch regions, which are stabilized through dimerization by means of domain-swapping in the crystals. In contrast, small-angle X-ray scattering measurements showed an extended monomer form of Rab27b in solution. The observed dimer formation of Rab27b-GDP in the crystals would restrain the highly flexible switch regions. Possible biological implications of this atypical structure of Rab27b and its plausible influence in effector interaction are discussed.
Chavas
Leonard M G
LM
Structural Biology Research Center, Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), Tsukuba, Ibaraki 305-0801, Japan.
Torii
Seiji
S
Kamikubo
Hironari
H
Kawasaki
Masato
M
Ihara
Kentaro
K
Kato
Ryuichi
R
Kataoka
Mikio
M
Izumi
Tetsuro
T
Wakatsuki
Soichi
S
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004220:Disulfides / Q000737:chemistry; D015870:Gene Expression; D047468:Immunoprecipitation; D008027:Light; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009705:Nucleosides / Q000378:metabolism; D011487:Protein Conformation; D012542:Scattering, Radiation; D012996:Solutions; D014965:X-Rays; D020691:rab GTP-Binding Proteins / Q000737:chemistry* / Q000235:genetics
D004220:Disulfides; D009705:Nucleosides; D012996:Solutions; C512958:Rab27b protein, mouse; D020691:rab GTP-Binding Proteins