Single-Molecule Folding Mechanism of an EF-Hand Neuronal Calcium Sensor (Articolo in rivista)

Type
Label
  • Single-Molecule Folding Mechanism of an EF-Hand Neuronal Calcium Sensor (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1016/j.str.2013.07.022 (literal)
Alternative label
  • Heidarsson, Petur O.; Otazo, Mariela R.; Bellucci, Luca; Mossa, Alessandro; Imparato, Alberto; Paci, Emanuele; Corni, Stefano; Di Felice, Rosa; Kragelund, Birthe B.; Cecconi, Ciro (2013)
    Single-Molecule Folding Mechanism of an EF-Hand Neuronal Calcium Sensor
    in Structure (Lond.)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Heidarsson, Petur O.; Otazo, Mariela R.; Bellucci, Luca; Mossa, Alessandro; Imparato, Alberto; Paci, Emanuele; Corni, Stefano; Di Felice, Rosa; Kragelund, Birthe B.; Cecconi, Ciro (literal)
Pagina inizio
  • 1812 (literal)
Pagina fine
  • 1821 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 21 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
  • 10 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 10 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • University of Copenhagen; Consiglio Nazionale delle Ricerche (CNR)NANO; Ctr Appl Technol & Nucl Dev CEADEN; Aarhus University; University of Leeds (literal)
Titolo
  • Single-Molecule Folding Mechanism of an EF-Hand Neuronal Calcium Sensor (literal)
Abstract
  • EF-hand calcium sensors respond structurally to changes in intracellular Ca2+ concentration, triggering diverse cellular responses and resulting in broad interactomes. Despite impressive advances in decoding their structure-function relationships, the folding mechanism of neuronal calcium sensors is still elusive. We used single-molecule optical tweezers to study the folding mechanism of the human neuronal calcium sensor 1 (NCS1). Two intermediate structures induced by Ca2+ binding to the EF-hands were observed during refolding. The complete folding of the C domain is obligatory for the folding of the N domain, showing striking interdomain dependence. Molecular dynamics results reveal the atomistic details of the unfolding process and rationalize the different domain stabilities during mechanical unfolding. Through constant-force experiments and hidden Markov model analysis, the free energy landscape of the protein was reconstructed. Our results emphasize that NCS1 has evolved a remarkable complex interdomain cooperativity and a fundamentally different folding mechanism compared to structurally related proteins. (literal)
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