6hka

The solution structure of the micelle-associated FATC domain of the human protein kinase ataxia telangiectasia mutated (ATM)

spinqualitylabelsall models 6hka, 20 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6hka is a 1 chain structure with sequence from Strsg. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: ATM (STRSG) Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The Ser/Thr protein kinase ataxia telangiectasia mutated (ATM) plays an important role in the DNA damage response, signaling in response to redox signals, the control of metabolic processes, and mitochondrial homeostasis. ATM localizes to the nucleus and at the plasma membrane, mitochondria, peroxisomes, and other cytoplasmic vesicular structures. It has been shown that the C-terminal FATC domain of human ATM (hATMfatc) can interact with a range of membrane mimetics and may thereby act as a membrane-anchoring unit. Here, NMR structural and 15N-relaxation data, NMR data using spin-labeled micelles, and MD simulations of micelle-associated hATMfatc revealed that it binds the micelle by a dynamic assembly of three helices with many residues of hATMfatc located in the head-group region. We observed that none of the three helices penetrates the micelle deeply or makes significant tertiary contacts to the other helices. NMR-monitored interaction experiments with hATMfatc variants in which two conserved aromatic residues (Phe-93 and Trp-96) were either individually or both replaced by alanine disclosed that the double substitution does not abrogate the interaction with micelles and bicelles at the high concentrations these aggregates are typically used, but impairs interactions with small unilamellar vesicles (SUVs), usually used at much lower lipid concentrations and considered a better mimetic for natural membranes. We conclude that the observed dynamic structure of micelle-associated hATMfatc may enable it to interact with differently composed membranes or membrane-associated interaction partners and thereby regulate ATM's kinase activity. Moreover, the FATC domain of ATM maybe function as membrane-anchoring unit for other biomolecules. NMR- and MD simulation-based structural characterization of the membrane-associating FATC domain of ataxia telangiectasia mutated.,Abd Rahim MS, Cherniavskyi YK, Tieleman DP, Dames SA J Biol Chem. 2019 Mar 13. pii: RA119.007653. doi: 10.1074/jbc.RA119.007653. PMID:30867195 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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