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Speculative model extending our results for INM-localized nesprin-1α to the ONM-localized nesprin-1 giant isoform. Adaptive domain (AD)-mediated self-folding and stabilization of dimers is predicted to form INM- and ONM-localized “knots” that mechanically secure and balance the formation of NE-spanning LINC complexes with SUN-domain protein dimers.
