Structural and functional insights into TBC1D17 highlight the importance of the previously uncharacterized
Dominika Nielipińska1, Marta Orlikowska2, Maciej Nielipiński1
1Institute of Molecular and Industrial Biotechnology, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Lodz, Poland.
Protein Science : a Publication of the Protein Society
|April 18, 2026
Summary
The TBC1D17 protein
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- TBC (Tre2/Bub2/Cdc16) domain-containing proteins are GTPase-activating proteins (GAPs) that regulate vesicle trafficking by interacting with Rab GTPases.
- TBC1D17 is a GAP involved in Shiga toxin trafficking, autophagy, and glucose metabolism.
Purpose of the Study:
- To determine the crystal structures of the TBC domains of murine and human TBC1D17.
- To investigate the interaction between TBC1D17 and Rab5a, focusing on the role of its Rab-binding domain (RBD).
Main Methods:
- X-ray crystallography to determine the 3D structures of TBC1D17 TBC domains.
- Protein fragment interaction assays to study TBC1D17 and Rab5a binding.
Main Results:
- The crystal structures of murine and human TBC1D17 TBC domains revealed a heart-like shape and dimerization.
- Dimerization involved a fragment near residues critical for GTP hydrolysis.
- Rab5a showed strong interactions with TBC1D17 fragments containing the RBD, but weak interactions with the TBC domain alone.
Conclusions:
- The TBC domain of TBC1D17 dimerizes and has a distinct structure.
- The uncharacterized Rab-binding domain (RBD) of TBC1D17 is crucial for its interaction with Rab5a, not the TBC domain itself.
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