title: CARP interacts with titin at a unique helical N2A sequence and at the domain Ig81 to form a structured complex.
abstract: The cardiac ankyrin repeat protein (CARP) is up-regulated in the myocardium during cardiovascular disease and in response to mechanical or toxic stress. Stress-induced CARP interacts with the N2A spring region of the titin filament to modulate muscle compliance. We characterize the interaction between CARP and titin-N2A and show that the binding site in titin spans the dual domain UN2A-Ig81. We find that the unique sequence UN2A is not structurally disordered, but that it has a stable, elongated α-helical fold that possibly acts as a constant force spring. Our findings portray CARP/titin-N2A as a structured node and help to rationalize the molecular basis of CARP mechanosensing in the sarcomeric I-band.
authors.affiliation: Department of Biology, University of Konstanz, Germany.|Institute of Integrative Biology, University of Liverpool, UK.
authors.forename: Tiankun
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Biology, University of Konstanz, Germany.|Institute of Integrative Biology, University of Liverpool, UK.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Fleming
authors.affiliation: Department of Biology, University of Konstanz, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.affiliation: Department of Integrative Pathophysiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Julius
authors.initials: J
authors.lastname: Bogomolovas
authors.affiliation: Institute of Integrative Biology, University of Liverpool, UK.
authors.forename: Igor
authors.initials: I
authors.lastname: Barsukov
authors.affiliation: Institute of Integrative Biology, University of Liverpool, UK.
authors.forename: Daniel J
authors.identifier: 0000-0002-7565-8937
authors.initials: DJ
authors.lastname: Rigden
authors.affiliation: Department of Integrative Pathophysiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Labeit
authors.affiliation: Department of Biology, University of Konstanz, Germany. olga.mayans@uni-konstanz.de.|Institute of Integrative Biology, University of Liverpool, UK. olga.mayans@uni-konstanz.de.
authors.forename: Olga
authors.initials: O
authors.lastname: Mayans
mesh_terms: D001665:Binding Sites; D064211:Connectin / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009124:Muscle Proteins / Q000737:chemistry* / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: C491304:ANKRD1 protein, human; D064211:Connectin; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins
keywords: SEC-MALLS; X-ray crystallography; circular dichroism; recombinant proteins; small-angle X-ray scattering