Exploring the folding landscape of leptin: Insights into threading pathways

Registro completo de metadados
MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversity of Warsaw-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorUniversity of Hawaii at Manoa-
Autor(es): dc.contributorScience and Technology of São Paulo (IFSP)-
Autor(es): dc.creatorda Silva, Fernando Bruno-
Autor(es): dc.creatorSimien, Jennifer M.-
Autor(es): dc.creatorViegas, Rafael G.-
Autor(es): dc.creatorHaglund, Ellinor-
Autor(es): dc.creatorLeite, Vitor Barbanti Pereira-
Data de aceite: dc.date.accessioned2025-08-21T22:54:58Z-
Data de disponibilização: dc.date.available2025-08-21T22:54:58Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2024-03-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1016/j.jsb.2023.108054-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/303953-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/303953-
Descrição: dc.descriptionThe discovery of new protein topologies with entanglements and loop-crossings have shown the impact of local amino acid arrangement and global three-dimensional structures. This phenomenon plays a crucial role in understanding how protein structure relates to folding and function, affecting the global stability, and biological activity. Protein entanglements encompassing knots and non-trivial topologies add complexity to their folding free energy landscapes. However, the initial native contacts driving the threading event for entangled proteins remains elusive. The Pierced Lasso Topology (PLT) represents an entangled topology where a covalent linker creates a loop in which the polypeptide backbone is threaded through. Compared to true knotted topologies, PLTs are simpler topologies where the covalent-loop persists in all conformations. In this work, the PLT protein leptin, is used to visualize and differentiate the preference for slipknotting over plugging transition pathways along the folding route. We utilize the Energy Landscape Visualization Method (ELViM), a multidimensional projection technique, to visualize and distinguish early threaded conformations that cannot be observed in an in vitro experiment. Critical contacts for the leptin threading mechanisms were identified where the competing pathways are determined by the formation of a hairpin loop in the unfolded basin. Thus, prohibiting the dominant slipknotting pathway. Furthermore, ELViM offers insights into distinct folding pathways associated with slipknotting and plugging providing a novel tool for de novo design and in vitro experiments with residue specific information of threading events in silico.-
Descrição: dc.descriptionCentre of New Technologies University of Warsaw, Banacha 2c-
Descrição: dc.descriptionInstitute of Biosciences Humanities and Exact Sciences (IBILCE) São Paulo State University (UNESP) São José do Rio Preto-
Descrição: dc.descriptionDepartment of Chemistry University of Hawaii at Manoa-
Descrição: dc.descriptionFederal Institute of Education Science and Technology of São Paulo (IFSP), SP-
Descrição: dc.descriptionInstitute of Biosciences Humanities and Exact Sciences (IBILCE) São Paulo State University (UNESP) São José do Rio Preto-
Idioma: dc.languageen-
Relação: dc.relationJournal of Structural Biology-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectEnergy landscape-
Palavras-chave: dc.subjectLeptin-
Palavras-chave: dc.subjectPierced Lasso Topology-
Palavras-chave: dc.subjectProtein folding-
Palavras-chave: dc.subjectTopology-
Título: dc.titleExploring the folding landscape of leptin: Insights into threading pathways-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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