title: α-Actinin/titin interaction: A dynamic and mechanically stable cluster of bonds in the muscle Z-disk.
abstract: Stable anchoring of titin within the muscle Z-disk is essential for preserving muscle integrity during passive stretching. One of the main candidates for anchoring titin in the Z-disk is the actin cross-linker α-actinin. The calmodulin-like domain of α-actinin binds to the Z-repeats of titin. However, the mechanical and kinetic properties of this important interaction are still unknown. Here, we use a dual-beam optical tweezers assay to study the mechanics of this interaction at the single-molecule level. A single interaction of α-actinin and titin turns out to be surprisingly weak if force is applied. Depending on the direction of force application, the unbinding forces can more than triple. Our results suggest a model where multiple α-actinin/Z-repeat interactions cooperate to ensure long-term stable titin anchoring while allowing the individual components to exchange dynamically.
authors.affiliation: Physik Department E22, Technische Universität München, 85748 Garching, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Grison
authors.affiliation: Physik Department E22, Technische Universität München, 85748 Garching, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Merkel
authors.affiliation: Department of Structural and Computational Biology, Max F. Perutz Laboratories, University of Vienna, A-1030 Vienna, Austria.
authors.forename: Julius
authors.initials: J
authors.lastname: Kostan
authors.affiliation: Department of Structural and Computational Biology, Max F. Perutz Laboratories, University of Vienna, A-1030 Vienna, Austria.|Department of Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, SI-1000 Ljubljana, Slovenia.
authors.forename: Kristina
authors.initials: K
authors.lastname: Djinović-Carugo
authors.affiliation: Physik Department E22, Technische Universität München, 85748 Garching, Germany; mrief@ph.tum.de.|Munich Center for Integrated Protein Science, 81377 Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Rief
mesh_terms: D000185:Actinin / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D064211:Connectin / Q000737:chemistry / Q000378:metabolism*; D003545:Cysteine / Q000737:chemistry; D003553:Cystine / Q000737:chemistry; D006801:Humans; D016297:Mutagenesis, Site-Directed; D052898:Optical Tweezers; D000072417:Protein Domains; D025941:Protein Interaction Mapping; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D012518:Sarcomeres / Q000737:chemistry / Q000648:ultrastructure; D013314:Stress, Mechanical
chemical_list: C401401:ACTN2 protein, human; D064211:Connectin; D011993:Recombinant Fusion Proteins; D000185:Actinin; D003553:Cystine; D003545:Cysteine
keywords: Z-disk mechanics; optical tweezers; titin Z-repeats; α-actinin