Structural Insights into $\mathrm{Ca^{2+}}$-Calmodulin Regulation of Plectin 1a-Integrin β4 Interaction in Hemidesmosomes

Song, Jae-Geun; Svergun, Dmitri I.; Warscheid, Bettina; Wiche, Gerhard; Djinović-Carugo, Kristina; Kostan, Julius; Drepper, Friedel; Konarev, Petr V.; Grishkovskaya, Irina; Gregor, Martin; Knapp, Bettina; de Almeida Ribeiro, Euripedes

doi:10.1016/j.str.2015.01.011

Journal Article

PUBDB-2016-00545

Structural Insights into $\mathrm{Ca^{2+}}$-Calmodulin Regulation of Plectin 1a-Integrin β4 Interaction in Hemidesmosomes

Song, J.-G. ; Kostan, J. ; Drepper, F. ; Knapp, B. ; de Almeida Ribeiro, E. ; Konarev, P.EMBL* ; Grishkovskaya, I. ; Wiche, G. ; Gregor, M. ; Svergun, D.EMBL* ; Warscheid, B. ; Djinović-Carugo, K. (Corresponding author)

2015
Elsevier Science London [u.a.]

Structure 23(3), 558 - 570 (2015) [10.1016/j.str.2015.01.011]

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Please use a persistent id in citations: doi:10.1016/j.str.2015.01.011

Abstract: The mechanical stability of epithelial cells, whichprotect organisms from harmful external factors, ismaintained by hemidesmosomes via the interactionbetween plectin 1a (P1a) and integrin a6b4. Bindingof calcium-calmodulin (Ca 2+ -CaM) to P1a togetherwith phosphorylation of integrin b4 disrupts thiscomplex, resulting in disassembly of hemidesmo-somes. We present structures of the P1a actin bind-ing domain either in complex with the N-ter lobe ofCa 2+ -CaM or with the first pair of integrin b4 fibro-nectin domains. Ca 2+ -CaM binds to the N-ter iso-form-specific tail of P1a in a unique manner, via itsN-ter lobe in an extended conformation. Structural,cell biology, and biochemical studies suggest thefollowing model: binding of Ca 2+ -CaM to an intrinsi-cally disordered N-ter segment of plectin convertsit to an a helix, which repositions calmodulin todisplace integrin b4 by steric repulsion. This modelcould serve as a blueprint for studies aimed at under-standing how Ca 2+ -CaM or EF-hand motifs regulateF-actin-based cytoskeleton.

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