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SARA and endofin are endosomal adaptor proteins that drive Smad phosphorylation by ligand-activated transforming growth factor β/bone morphogenetic protein (TGFβ/BMP) receptors. We show in this study that SARA and endofin also recruit the tumor supressor HD-PTP, a master regulator of endosomal sorting and ESCRT-dependent receptor downregulation. High-affinity interactions occur between the SARA/endofin N termini, and the conserved hydrophobic region in the HD-PTP Bro1 domain that binds CHMP4/ESCRT-III. CHMP4 engagement is a universal feature of Bro1 proteins, but SARA/endofin binding is specific to HD-PTP. Crystallographic structures of HD-PTPBro1 in complex with SARA, endofin, and three CHMP4 isoforms revealed that all ligands bind similarly to the conserved site but, critically, only SARA/endofin interact at a neighboring pocket unique to HD-PTP. The structures, together with mutagenesis and binding analysis, explain the high affinity and specific binding of SARA/endofin, and why they compete so effectively with CHMP4. Our data invoke models for how endocytic regulation of TGFβ/BMP signaling is controlled.
Pubmed ID: 28602823 RIS Download
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Portal for Macromolecular X-Ray Crystallography to produce and support an integrated suite of programs that allows researchers to determine macromolecular structures by X-ray crystallography, and other biophysical techniques. Used in the education and training of scientists in experimental structural biology for determination and analysis of protein structure.
View all literature mentionsWeb tool as secondary structure prediction method, incorporating two feed forward neural networks which perform analysis on output obtained from PSI-BLAST. Web server offering analyses of protein sequences.
View all literature mentionsSoftware for macromolecular model building, model completion and validation, and protein modelling using X-ray data. Coot displays maps and models and allows model manipulations such as idealization, rigid-body fitting, ligand search, Ramachandran plots, non-crystallographic symmetry and more. Source code is available.
View all literature mentionsA structure-validation web application which provides an expert-system consultation about the accuracy of a macromolecular structure model, diagnosing local problems and enabling their correction. MolProbity works best as an active validation tool (used as soon as a model is available and during each rebuild/refine loop) and when used for protein and RNA crystal structures, but it may also work well for DNA, ligands and NMR ensembles. It produces coordinates, graphics, and numerical evaluations that integrate with either manual or automated use in systems such as PHENIX, KiNG, or Coot.
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal targets ZFYVE16
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis polyclonal targets PTPN23
View all literature mentionsThis monoclonal targets HA
View all literature mentionsThis monoclonal targets polyHistidine
View all literature mentionsThis monoclonal targets c-Myc
View all literature mentionsThis monoclonal targets HA-Tag
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsA Python-based software suite for the automated determination of molecular structures using X-ray crystallography and other methods. Phenix includes programs for assessing data quality, experimental phasing, molecular replacement, model building, structure refinement, and validation. It also includes tools for reflection data and creating maps and models. Phenix can also be used for neutron crystallography. Tutorials and examples are available in the documentation tab.
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis monoclonal targets HA-Tag
View all literature mentionsThis polyclonal targets ZFYVE16
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis polyclonal targets PTPN23
View all literature mentionsThis monoclonal targets HA
View all literature mentionsThis monoclonal targets c-Myc
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