title: Spontaneous dimerization of titin protein Z1Z2 domains induces strong nanomechanical anchoring.
abstract: Muscle elasticity strongly relies on the mechanical anchoring of the giant protein titin to both the sarcomere M-band and the Z-disk. Such strong attachment ensures the reversible dynamics of the stretching-relaxing cycles determining the muscle passive elasticity. Similarly, the design of biomaterials with enhanced elastic function requires experimental strategies able to secure the constituent molecules to avoid mechanical failure. Here we show that an engineered titin-mimicking protein is able to spontaneously dimerize in solution. Our observations reveal that the titin Z1Z2 domains are key to induce dimerization over a long-range distance in proteins that would otherwise remain in their monomeric form. Using single molecule force spectroscopy, we measure the threshold force that triggers the noncovalent transition from protein dimer to monomer, occurring at ∼700 piconewtons. Such extremely high mechanical stability is likely to be a natural protective mechanism that guarantees muscle integrity. We propose a simple molecular model to understand the force-induced dimer-to-monomer transition based on the geometric distribution of forces occurring within a dimeric protein under mechanical tension.
authors.affiliation: Department of Physics and Randall Division of Cell and Molecular Biophysics, King's College London, London WC2R 2LS, United Kingdom. sergi.garcia-manyes@kcl.ac.uk
authors.forename: Sergi
authors.initials: S
authors.lastname: Garcia-Manyes
authors.forename: Carmen L
authors.initials: CL
authors.lastname: Badilla
authors.forename: Jorge
authors.initials: J
authors.lastname: Alegre-Cebollada
authors.forename: Yalda
authors.initials: Y
authors.lastname: Javadi
authors.forename: Julio M
authors.initials: JM
authors.lastname: Fernández
mesh_terms: D064211:Connectin; D006801:Humans; D009124:Muscle Proteins / Q000737:chemistry* / Q000235:genetics; D015202:Protein Engineering / Q000592:standards; D011494:Protein Kinases / Q000737:chemistry* / Q000235:genetics; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary
chemical_list: D064211:Connectin; D009124:Muscle Proteins; C577285:TTN protein, human; D011494:Protein Kinases