Database accession: MF7000704
Name: F-BAR domain of PSTIPIP1
PDB ID: 7aan
Experimental method: X-ray (2.14 Å)
Assembly: Homodimer
Source organism: Homo sapiens
Primary publication of the structure:
Manso JA, Marcos T, Ruiz-Martín V, Casas J, Alcón P, Sánchez Crespo M, Bayón Y, de Pereda JM, Alonso A
PSTPIP1-LYP phosphatase interaction: structural basis and implications for autoinflammatory disorders.
(2022) Cell. Mol. Life Sci. 79: 131
PMID: 35152348
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.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
actin filament binding actin filament binding
identical protein binding identical protein binding
Biological process:
actin filament polymerization actin filament polymerization
cell adhesion cell adhesion
endocytosis endocytosis
inflammatory response inflammatory response
innate immune response innate immune response
signal transduction signal transduction
Cellular component:
actin filament actin filament
cleavage furrow cleavage furrow
cytoplasm cytoplasm
cytosol cytosol
lamellipodium lamellipodium
membrane membrane
perinuclear region of cytoplasm perinuclear region of cytoplasm
plasma membrane plasma membrane
uropod uropod
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, B
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: Proline-serine-threonine phosphatase-interacting protein 1
Source organism: Homo sapiens
Length: 416 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMMPQLQFKDAFWCRDFTAHTGYEVLLQRLLDGRKMCKDMEELLRQRAQAEERYGKELVQIARKAGGQTEINSLRASFDSLKQQMENVGSSHIQLALTLREELRSLEEFRERQKEQRKKYEAVMDRVQKSKLSLYKKAMESKKTYEQKCRDADDAEQAFERISANGHQKQVEKSQNKARQCKDSATEAERVYRQSIAQLEKVRAEWEQEHRTTCEAFQLQEFDRLTILRNALWVHSNQLSMQCVKDDELYEEVRLTLEGCSIDADIDSFIQAKSTGTEPPAPVPYQNYYDREVTPLTSSPGIQPSCGMIKRFSGLLHGSPKTTSLAASAASTETLTPTPERNEGVYTAIAVQEIQGNPASPAQEYRALYDYTAQNPDELDLSAGDILEVILEGEDGWWTVERNGQRGFVPGSYLEKL
UniProtKB AC: O43586 (positions: 5-289)
Coverage: 68%
Name: Proline-serine-threonine phosphatase-interacting protein 1
Source organism: Homo sapiens
Length: 416 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMMPQLQFKDAFWCRDFTAHTGYEVLLQRLLDGRKMCKDMEELLRQRAQAEERYGKELVQIARKAGGQTEINSLRASFDSLKQQMENVGSSHIQLALTLREELRSLEEFRERQKEQRKKYEAVMDRVQKSKLSLYKKAMESKKTYEQKCRDADDAEQAFERISANGHQKQVEKSQNKARQCKDSATEAERVYRQSIAQLEKVRAEWEQEHRTTCEAFQLQEFDRLTILRNALWVHSNQLSMQCVKDDELYEEVRLTLEGCSIDADIDSFIQAKSTGTEPPAPVPYQNYYDREVTPLTSSPGIQPSCGMIKRFSGLLHGSPKTTSLAASAASTETLTPTPERNEGVYTAIAVQEIQGNPASPAQEYRALYDYTAQNPDELDLSAGDILEVILEGEDGWWTVERNGQRGFVPGSYLEKL
UniProtKB AC: O43586 (positions: 4-289)
Coverage: 68%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: F-BAR domain
Evidence level: Direct evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
F-BAR domains form an intimately packed six-helix bundle and bury a large, hydrophobic dimerization interface. They exist as dimers in solution, with no evidence for monomeric forms (PMID:17512409). Other BAR domains (N-BAR) displayed a two-state equilibrium unfolding (PMID:26368922, PMID:34423187).
Chain A:
N/A
Chain B:
N/A
Surface and contacts features:
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). Download the CIF file (.cif)
Download this entry's XML file (.xml)
Download this entry's JSON file (.json)
