2026-06-14T03:33:22Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/99312024-09-27T08:14:44Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Manteca, Aitor author Schönfelder, Jörg author Alonso-Caballero, Alvaro author Fertin, Marie J author Barruetabeña, Nerea author Faria, Bruna F author Herrero-Galan, Elas author Alegre-Cebollada, Jorge author De Sancho, David author Perez-Jimenez, Raul author 2017-08 The sarcomere-based structure of muscles is conserved among vertebrates; however, vertebrate muscle physiology is extremely diverse. A molecular explanation for this diversity and its evolution has not been proposed. We use phylogenetic analyses and single-molecule force spectroscopy (smFS) to investigate the mechanochemical evolution of titin, a giant protein responsible for the elasticity of muscle filaments. We resurrect eight-domain fragments of titin corresponding to the common ancestors to mammals, sauropsids, and tetrapods, which lived 105-356 Myr ago, and compare them with titin fragments from some of their modern descendants. We demonstrate that the resurrected titin molecules are rich in disulfide bonds and display high mechanical stability. These mechanochemical elements have changed over time, creating a paleomechanical trend that seems to correlate with animal body size, allowing us to estimate the sizes of extinct species. We hypothesize that mechanical adjustments in titin contributed to physiological changes that allowed the muscular development and diversity of modern tetrapods. Nat Struct Mol Biol. 2017; 24(8):652-657 10.1038/nsmb.3426 1545-9985 1545-9993 Nature structural & molecular biology 28671667 http://hdl.handle.net/20.500.12105/9931 Mechanochemical evolution of the giant muscle protein titin as inferred from resurrected proteins