Abstract 3051 The C2 domain augments Ras GTPase Activating Protein catalytic activity
Regulation of Ras GTPases by GTPase activating proteins (GAP) is essential for their normal signaling. Nine of the ten GAPs for Ras contain a C2 domain immediately proximal to their canonical GAP domain, and in RasGAP (p120GAP, p120RasGAP; RASA1) mutation of this domain is associated with vascular malformations in humans. Here, we show that the C2 domain of RasGAP is required for full catalytic activity towards Ras. Analysis of the RasGAP C2-GAP crystal structure, AlphaFold models, and sequence conservation reveal direct C2 domain interaction with the Ras allosteric lobe.
Authors
- Thomas L. Saunders (ORCID: https://orcid.org/0000-0003-2015-101X)
- Titus J. Boggon (ORCID: https://orcid.org/0000-0003-2862-1637)
- Kimberly J. Vish (ORCID: https://orcid.org/0000-0002-9394-1218)
- Manoj Paul
- Nathaniel L. Lartey (ORCID: https://orcid.org/0000-0002-9810-2720)
- Zachary T. Freeman (ORCID: https://orcid.org/0000-0003-1291-382X)
- Philip D. King (ORCID: https://orcid.org/0000-0002-5598-2748)
- Amy L. Stiegler (ORCID: https://orcid.org/0000-0003-0453-6104)
- Di Chen (ORCID: https://orcid.org/0000-0002-5202-566X)
Institutions
- Yale University (US)
Publication Details
- Journal
- Journal of Biological Chemistry
- Published
- 2025-05-01
- DOI
- https://doi.org/10.1016/j.jbc.2025.110138
- Primary Topic
- Protein Kinase Regulation and GTPase Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.00