2ZET

Crystal structure of the small GTPase Rab27B complexed with the Slp homology domain of Slac2-a/melanophilin

Summary for 2ZET

• Entry DOI: 10.2210/pdb2zet/pdb
• Descriptor: Ras-related protein Rab-27B, Melanophilin, MAGNESIUM ION, ... (7 entities in total)
• Functional Keywords: complex, gtp-binding protein, gtpase, g-protein, rab, rab27b, effector, melanophilin, slp homology domain, acetylation, lipoprotein, membrane, methylation, nucleotide-binding, prenylation, coiled coil, metal-binding, zinc, zinc-finger, structural genomics, nppsfa, national project on protein structural and functional analyses, riken structural genomics/proteomics initiative, rsgi, signaling protein
• Biological source: Mus musculus (mouse); More
• Cellular location: Membrane; Lipid-anchor (By similarity): Q99P58; Melanosome: Q91V27
• Total number of polymer chains: 4
• Total formula weight: 83463.62

Authors

Kukimoto-Niino, M.,Sakamoto, A.,Kanno, E.,Hanawa-Suetsugu, K.,Terada, T.,Shirouzu, M.,Fukuda, M.,Yokoyama, S.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2007-12-17, release date: 2008-09-30, Last modification date: 2024-10-23)

Primary citation

Kukimoto-Niino, M.,Sakamoto, A.,Kanno, E.,Hanawa-Suetsugu, K.,Terada, T.,Shirouzu, M.,Fukuda, M.,Yokoyama, S.
Structural basis for the exclusive specificity of Slac2-a/melanophilin for the Rab27 GTPases.
Structure, 16:1478-1490, 2008

PubMed Abstract: Rab27A is required for actin-based melanosome transport in mammalian skin melanocytes through its interaction with a specific effector, Slac2-a/melanophilin. Mutations that disrupt the Rab27A/Slac2-a interaction cause human Griscelli syndrome. The other Rab27 isoform, Rab27B, also binds all of the known effectors of Rab27A. In this study, we determined the crystal structure of the constitutively active form of Rab27B complexed with GTP and the effector domain of Slac2-a. The Rab27B/Slac2-a complex exhibits several intermolecular hydrogen bonds that were not observed in the previously reported Rab3A/rabphilin complex. A Rab27A mutation that disrupts one of the specific hydrogen bonds with Slac2-a resulted in the dramatic reduction of Slac2-a binding activity. Furthermore, we generated a Rab3A mutant that acquires Slac2-a binding ability by transplanting four Rab27-specific residues into Rab3A. These findings provide the structural basis for the exclusive association of Slac2-a with the Rab27 subfamily, whereas rabphilin binds several subfamilies, including Rab3 and Rab27.

PubMed: 18940604
DOI: 10.1016/j.str.2008.07.014

Experimental method

X-RAY DIFFRACTION (3 Å)