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

2024-01-08T14:45:01Z urn:hdl:10324/64306 PSTPIP1-LYP phosphatase interaction: structural basis and implications for autoinflammatory disorders 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 Producción Científica 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. 2024-01-08T14:45:01Z 2024-01-08T14:45:01Z 2022 info:eu-repo/semantics/article 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 eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/4.0/ Atribución 4.0 Internacional