TAILIEUCHUNG - Báo cáo khoa học: The intracellular region of the Notch ligand Jagged-1 gains partial structure upon binding to synthetic membranes

Notch ligands are membrane-spanning proteins made of a large extracellu-lar region, a transmembrane segment, and a 100–200 residue cytoplasmic tail. The intracellular region of Jagged-1, one of the five ligands to Notch receptors in man, mediates protein–protein interactions through the C-ter-minal PDZ binding motif, is involved in receptor⁄ligand endocytosis trig-gered by mono-ubiquitination, | ỊFEBS Journal The intracellular region of the Notch ligand Jagged-1 gains partial structure upon binding to synthetic membranes Matija Popovic Alfredo De Biasio Alessandro Pintar and Sandor Pongor Protein Structure and Bioinformatics Group InternationalCentre for Genetic Engineering and Biotechnology ICGEB Padriciano Trieste Italy Keywords membrane cytoplasm interface regulated intramembrane proteolysis SDS micelles phospholipid vesicles in-cellNMR Correspondence A. Pintar and S. Pongor Protein Structure and Bioinformatics Group International Centre for Genetic Engineering and Biotechnology ICGEB AREA Science Park Padriciano 99 I-34012 Trieste Italy Fax 39 040226555 Tel 39 0403757354 E-mail pintar@ pongor@ Received 15 June 2007 revised 8 August 2007 accepted 20 August 2007 doi Notch ligands are membrane-spanning proteins made of a large extracellular region a transmembrane segment and a 100-200 residue cytoplasmic tail. The intracellular region of Jagged-1 one of the five ligands to Notch receptors in man mediates protein-protein interactions through the C-ter-minal PDZ binding motif is involved in receptor ligand endocytosis triggered by mono-ubiquitination and as a consequence of regulated intramembrane proteolysis can be released into the cytosol as a signaling fragment. The intracellular region of Jagged-1 may then exist in at least two forms as a membrane-tethered protein located at the interface between the membrane and the cytoplasm and as a soluble nucleocytoplasmic protein. Here we report the characterization in different environments of a recombinant protein corresponding to the human Jagged-1 intracellular region J1_tmic . In solution J1_tmic behaves as an intrinsically disordered protein but displays a significant helical propensity. In the presence of SDS micelles and phospholipid vesicles used to mimick the interface between the plasma membrane and the cytosol J1_tmic undergoes a substantial .

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