Distinct Rab-binding domains mediate the interaction of Rabaptin-5 with GTP-bound Rab4 and Rab5.
Rabaptin-5 functions as an effector for the small GTPase Rab5, a regulator of endocytosis and early endosome fusion. We have searched for structural determinants that confer functional specificity on Rabaptin-5. Here we report that native cytosolic Rabaptin-5 is present in a homodimeric state and dimerization depends upon the presence of ... its coiled-coil predicted sequences. A 73 residue C-terminal region of Rabaptin-5 is necessary and sufficient both for the interaction with Rab5 and for Rab5-dependent recruitment of the protein on early endosomes. Surprisingly, we uncovered the presence of an additional Rab-binding domain at the N-terminus of Rabaptin-5. This domain mediates the direct interaction with the GTP-bound form of Rab4, a small GTPase that has been implicated in recycling from early endosomes to the cell surface. Based on these results, we propose that Rabaptin-5 functions as a molecular linker between two sequentially acting GTPases to coordinate endocytic and recycling traffic.
Mesh Terms:
Amino Acid Sequence, Animals, Cattle, Cell Line, Cricetinae, Cytosol, Dimerization, Endosomes, GTP-Binding Proteins, Guanosine Triphosphate, Hela Cells, Humans, Membrane Proteins, Molecular Sequence Data, Protein Binding, Protein Structure, Secondary, Recombinant Fusion Proteins, Sequence Alignment, Vesicular Transport Proteins, rab4 GTP-Binding Proteins, rab5 GTP-Binding Proteins
Amino Acid Sequence, Animals, Cattle, Cell Line, Cricetinae, Cytosol, Dimerization, Endosomes, GTP-Binding Proteins, Guanosine Triphosphate, Hela Cells, Humans, Membrane Proteins, Molecular Sequence Data, Protein Binding, Protein Structure, Secondary, Recombinant Fusion Proteins, Sequence Alignment, Vesicular Transport Proteins, rab4 GTP-Binding Proteins, rab5 GTP-Binding Proteins
EMBO J.
Date: Apr. 01, 1998
PubMed ID: 9524117
View in: Pubmed Google Scholar
Download Curated Data For This Publication
6987
Switch View:
- Interactions 10