Journal Article

PUBDB-2026-01406

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Structural and functional insights into TBC1D17 highlight the importance of the previously uncharacterized Rab‐binding domain

Nielipińska, D. ; Orlikowska, M. ; Nielipiński, M. ; Sekuła, B. ; Błażewska, K. M. ; Gendaszewska-Darmach, E. ; Pietrzyk-Brzezińska, A. J. (Corresponding author)

2026
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/pro.70581  doi:10.3204/PUBDB-2026-01406

Abstract: TBC (Tre2/Bub2/Cdc16) domain-containing proteins constitute the widespread family of GTPase-activating proteins (GAPs). They interact with the Rab superfamily of small GTPases, stimulate GTP hydrolysis, and regulate vesicle trafficking. TBC1D17, involved in Shiga toxin trafficking, autophagy and glucose metabolism regulation, constitutes an example of GAP interacting with Rabs. Here we present the first crystal structures of the murine and human TBC domains of TBC1D17 proteins determined at 2.20 and 3.34 Å resolution, respectively. The TBC domain in both structures represents a heart-like shape. Our analyses revealed dimerization of the TBC domain through a fragment located near residues participating in GTP hydrolysis, a result we observed also in structures of closely related homologs. Furthermore, we tested Rab5a interactions with various fragments of TBC1D17. Interestingly, this protein contains an annotated, yet uncharacterized, Rab-binding domain (RBD) and our studies revealed strong interactions of Rab5a with TBC1D17 fragments containing RBD, while interactions with the TBC domain alone are much weaker. These results provide the first direct evidence for the critical role of the TBC1D17 RBD in interactions with Rab5a.

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Contributing Institute(s):

1. EMBL-User (EMBL-User)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)

Experiment(s):

1. PETRA Beamline P13 (PETRA III)

Appears in the scientific report 2026

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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