TY - JOUR
AU - Song, Jae-Geun
AU - Kostan, Julius
AU - Drepper, Friedel
AU - Knapp, Bettina
AU - de Almeida Ribeiro, Euripedes
AU - Konarev, Petr V.
AU - Grishkovskaya, Irina
AU - Wiche, Gerhard
AU - Gregor, Martin
AU - Svergun, Dmitri I.
AU - Warscheid, Bettina
AU - Djinović-Carugo, Kristina
TI - Structural Insights into Ca<sup>2+</sup>-Calmodulin Regulation of Plectin 1a-Integrin β4 Interaction in Hemidesmosomes
JO - Structure
VL - 23
IS - 3
SN - 0969-2126
CY - London [u.a.]
PB - Elsevier Science
M1 - PUBDB-2016-00545
SP - 558 - 570
PY - 2015
AB - 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.
LB - PUB:(DE-HGF)16
UR - <Go to ISI:>//WOS:000350886100014
C6 - pmid:25703379
DO - DOI:10.1016/j.str.2015.01.011
UR - https://bib-pubdb1.desy.de/record/293456
ER -