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PreprintCC BYbioRxiv

BCAS3 regulates WIPI2b via a direct interaction in the ATG16L1-binding cleft

  • P. Rosewell
  • A. Üffing
  • L. Masino
  • S. A. Tooze1
  1. 1The Francis Crick Institute
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Abstract

De novo formation of the phagophore membrane is a fundamental step in autophagy and relies on recruitment of the E3-like ligase complex via an interaction between ATG16L1 and phosphatidylinositol 3-phosphate (PtdIns3P)-effector protein, WIPI2b. Although WIPI2b can directly bind membranes, how its membrane association is regulated is still not fully understood. Here, we describe BCAS3 as a novel direct interactor of WIPI2b and demonstrate that a peptide of BCAS3 binds in the ATG16L1-binding cleft of WIPI2b with low micromolar affinity. We show that BCAS3 and its partner PHAF1 induce recruitment of WIPI2b to membranes via the interaction of BCAS3 with PtdIns3P. This not only challenges the current paradigm, whereby ATG16L1 is the only confirmed binder of WIPI2b in this region, but also offers a mechanism through which WIPI2b membrane association might be regulated.

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Cite

BibTeXRIS
BibTeX
@misc{rosewell2026bcas3,
  title = {{BCAS3 regulates WIPI2b via a direct interaction in the ATG16L1-binding cleft}},
  author = {P. Rosewell and A. Üffing and L. Masino and S. A. Tooze},
  howpublished = {bioRxiv},
  year = {2026},
  month = nov,
  doi = {10.64898/2026.11.06.764939},
  url = {https://www.biorxiv.org/content/10.64898/2026.11.06.764939v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - BCAS3 regulates WIPI2b via a direct interaction in the ATG16L1-binding cleft
AU  - P. Rosewell
AU  - A. Üffing
AU  - L. Masino
AU  - S. A. Tooze
PY  - 2026
DA  - 2026/11/06
PB  - bioRxiv
DO  - 10.64898/2026.11.06.764939
UR  - https://www.biorxiv.org/content/10.64898/2026.11.06.764939v1
AB  - De novo formation of the phagophore membrane is a fundamental step in autophagy and relies on recruitment of the E3-like ligase complex via an interaction between ATG16L1 and phosphatidylinositol 3-phosphate (PtdIns3P)-effector protein, WIPI2b. Although WIPI2b can directly bind membranes, how its membrane association is regulated is still not fully understood. Here, we describe BCAS3 as a novel direct interactor of WIPI2b and demonstrate that a peptide of BCAS3 binds in the ATG16L1-binding cleft of WIPI2b with low micromolar affinity. We show that BCAS3 and its partner PHAF1 induce recruitment of WIPI2b to membranes via the interaction of BCAS3 with PtdIns3P. This not only challenges the current paradigm, whereby ATG16L1 is the only confirmed binder of WIPI2b in this region, but also offers a mechanism through which WIPI2b membrane association might be regulated.
ER  -