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The recently published novel integrinaIIbb3 ectodomain crystallographic structure and NMR structures of its transmembrane⁄cytoplasmic segments were employed to refine previously developed molecular models. Alterna-tive complete aIIbb3 models were built and evaluated, and their shape was compared with EM maps and their computed hydrodynamic⁄conforma-tional properties were compared with the available experimental data. | ễFEBS Journal Solution properties of full-length integrin aIIbp3 refined models suggest environment-dependent induction of alternative bent extended resting states Camillo Rosano1 and Mattia Rocco2 1 Nanobiotecnologie Istituto Nazionale per la Ricerca sulCancro 1ST Genova Italy 2 Biopolimeri e Proteomica IST Genova Italy Keywords blood coagulation hydrodynamics modeling modular proteins protein structure Correspondence M. Rocco Biopolimeri e Proteomica IST c o CBA Largo R. Benzi 10 I-16132 Genova Italy Fax 39-0105737-325 Tel 39-0105737-310 E-mail mattia.rocco@istge.it Received 12 November 2009 revised 1 May 2010 accepted 29 May 2010 doi 10.1111 j.1742-4658.2010.07724.x The recently published novel integrin aIIbp3 ectodomain crystallographic structure and NMR structures of its transmembrane cytoplasmic segments were employed to refine previously developed molecular models. Alternative complete aIIbp3 models were built and evaluated and their shape was compared with EM maps and their computed hydrodynamic conforma-tional properties were compared with the available experimental data. A partially extended closed model or a mixture of bent closed and exten-ded closed conformations are both compatible with the results of a recent small-angle neutron scattering study of Triton X-100-solubilized resting aIIbp3 while new electron microscopy evidence of nanodiscs-embedded aIIbp3 supports the bent closed resting form. However only an extended -closed model matches well the hydrodynamics of either octyl-glucoside-sol-ubilized or nanodiscs-embedded resting aIIbp3 suggesting that different solubilization strategies and substrate interactions might operate a conformational selection between alternative stable states. Furthermore extende-d open models are required to match the electron tomography map and the hydrodynamics following the priming-induced b3 hybrid domain swing-out but without immediate full tail separation. Importantly both extension and opening transitions can occur
