7zx4

Clathrin N-terminal domain in complex with a HURP phospho-peptide

spinqualitylabelsall models 7zx4, resolution 2.08Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7zx4 is a 5 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.08Å Ligands: CL, GOL, NA, SEP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease CLH1_HUMAN Translocation renal cell carcinoma;Inflammatory myofibroblastic tumor. Function CLH1_HUMAN Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi network. Publication Abstract from PubMed Phosphorylation is a ubiquitous post-translation modification that regulates protein function by promoting, inhibiting or modulating protein-protein interactions. Hundreds of thousands of phosphosites have been identified but the vast majority have not been functionally characterised and it remains a challenge to decipher phosphorylation events modulating interactions. We generated a phosphomimetic proteomic peptide-phage display library to screen for phosphosites that modulate short linear motif-based interactions. The peptidome covers ~13,500 phospho-serine/threonine sites found in the intrinsically disordered regions of the human proteome. Each phosphosite is represented as wild-type and phosphomimetic variant. We screened 71 protein domains to identify 248 phosphosites that modulate motif-mediated interactions. Affinity measurements confirmed the phospho-modulation of 14 out of 18 tested interactions. We performed a detailed follow-up on a phospho-dependent interaction between clathrin and the mitotic spindle protein hepatoma-upregulated protein (HURP), demonstrating the essentiality of the phospho-dependency to the mitotic function of HURP. Structural characterisation of the clathrin-HURP complex elucidated the molecular basis for the phospho-dependency. Our work showcases the power of phosphomimetic ProP-PD to discover novel phospho-modulated interactions required for cellular function. Large-scale phosphomimetic screening identifies phospho-modulated motif-based protein interactions.,Kliche J, Garvanska DH, Simonetti L, Badgujar D, Dobritzsch D, Nilsson J, Davey NE, Ivarsson Y Mol Syst Biol. 2023 Jul 11;19(7):e11164. doi: 10.15252/msb.202211164. Epub 2023 , May 23. PMID:37219487 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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