title: Multidomain proteins under force.
abstract: Advancements in single-molecule force spectroscopy techniques such as atomic force microscopy and magnetic tweezers allow investigation of how domain folding under force can play a physiological role. Combining these techniques with protein engineering and HaloTag covalent attachment, we investigate similarities and differences between four model proteins: I10 and I91-two immunoglobulin-like domains from the muscle protein titin, and two α + β fold proteins-ubiquitin and protein L. These proteins show a different mechanical response and have unique extensions under force. Remarkably, when normalized to their contour length, the size of the unfolding and refolding steps as a function of force reduces to a single master curve. This curve can be described using standard models of polymer elasticity, explaining the entropic nature of the measured steps. We further validate our measurements with a simple energy landscape model, which combines protein folding with polymer physics and accounts for the complex nature of tandem domains under force. This model can become a useful tool to help in deciphering the complexity of multidomain proteins operating under force.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY, United States of America.
authors.forename: Jessica
authors.initials: J
authors.lastname: Valle-Orero
authors.forename: Jaime Andrés
authors.initials: JA
authors.lastname: Rivas-Pardo
authors.forename: Ionel
authors.initials: I
authors.lastname: Popa
mesh_terms: D064211:Connectin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019277:Entropy; D018625:Microscopy, Atomic Force / Q000379:methods*; D000072417:Protein Domains; D015202:Protein Engineering / Q000379:methods; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D064211:Connectin; D011994:Recombinant Proteins; D025801:Ubiquitin