7AAL

Crystal structure of the F-BAR domain of PSTIPIP1, G258A mutant

Summary for 7AAL

• Entry DOI: 10.2210/pdb7aal/pdb
• Related: 7AAM 7AAN
• Descriptor: Proline-serine-threonine phosphatase-interacting protein 1 (2 entities in total)
• Functional Keywords: pyogenic arthritis, pyoderma gangrenosum and acne (papa), inflammatory response, membrane binding, signaling protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 68549.12

Authors

Manso, J.A.,Alcon, P.,Bayon, Y.,Alonso, A.,de Pereda, J.M. (deposition date: 2020-09-04, release date: 2022-02-23, Last modification date: 2024-02-07)

Primary citation

Manso, J.A.,Marcos, T.,Ruiz-Martin, V.,Casas, J.,Alcon, P.,Sanchez Crespo, M.,Bayon, Y.,de Pereda, J.M.,Alonso, A.
PSTPIP1-LYP phosphatase interaction: structural basis and implications for autoinflammatory disorders.
Cell.Mol.Life Sci., 79:131-131, 2022

PubMed Abstract: 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.

PubMed: 35152348
DOI: 10.1007/s00018-022-04173-w

Experimental method

X-RAY DIFFRACTION (1.97 Å)