http://www.cnr.it/ontology/cnr/individuo/prodotto/ID313468
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)
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- 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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