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Mammalian genomes are organized into megabase-scale topologically associated domains (TADs). We demonstrate that disruption of TADs can rewire long-range regulatory architecture and result in pathogenic phenotypes. We show that distinct human limb malformations are caused by deletions, inversions, or duplications altering the structure of the TAD-spanning WNT6/IHH/EPHA4/PAX3 locus. Using CRISPR/Cas...
Activation of the ligand binding function of integrin heterodimers requires transmission of an ''inside-out'' signal from their small intracellular segments to their large extracellular domains. The structure of the cytoplasmic domain of a prototypic integrin α IIb β 3 has been solved by NMR and reveals multiple hydrophobic and electrostatic contacts within the membrane-proximal...
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