2026-04-14T18:22:52Zhttps://uvadoc.uva.es/oai/request

oai:uvadoc.uva.es:10324/643062025-09-10T10:49:53Zcom_10324_1134com_10324_931com_10324_894col_10324_1213

Manso, José A. Marcos, Tamara Ruiz Martín, Virginia Casas Requena, Javier Alcón, Pablo Sánchez Crespo, Mariano Bayón Prieto, Yolanda de Pereda, José M. Alonso, Andrés 2024-01-08T14:45:01Z 2024-01-08T14:45:01Z 2022 Cell Mol Life Sci 79:131. https://doi.org/10.1007/s00018-022-04173-w 1420-682X https://uvadoc.uva.es/handle/10324/64306 10.1007/s00018-022-04173-w 2 Cellular and Molecular Life Sciences 79 1420-9071 Mutations in the adaptor protein PSTPIP1 cause a spectrum of autoinflammatory diseases, including PAPA and PAMI; however, the mechanism underlying these diseases remains unknown. Most of these mutations lie in PSTPIP1 F-BAR domain, which binds to LYP, a protein tyrosine phosphatase associated with arthritis and lupus. To shed light on the mechanism by which these mutations generate autoinflammatory disorders, we solved the structure of the F-BAR domain of PSTPIP1 alone and bound to the C-terminal homology segment of LYP, revealing a novel mechanism of recognition of Pro-rich motifs by proteins in which a single LYP molecule binds to the PSTPIP1 F-BAR dimer. The residues R228, D246, E250, and E257 of PSTPIP1 that are mutated in immunological diseases directly interact with LYP. These findings link the disruption of the PSTPIP1/LYP interaction to these diseases, and support a critical role for LYP phosphatase in their pathogenesis. eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/4.0/ Atribución 4.0 Internacional PSTPIP1-LYP phosphatase interaction: structural basis and implications for autoinflammatory disorders info:eu-repo/semantics/article