120024 20240319081004.0 doi 10.1002/pro.4445 sideral 130822 ART-2022-130822 eng Galano-Frutos, Juan José Universidad de Zaragoza (orcid)0000-0002-1896-7805 A look at the face of the molten globule: Structural model of the <scp> <i>Helicobacter pylori</i> </scp> apoflavodoxin ensemble at acidic <scp>pH</scp> 2022 Access copy available to the general public Unrestricted Molten globule (MG) is the name given to acompact, non-native conformation ofproteins that has stimulated the imagination and work in the protein folding fieldfor more than 40 years. The MG has been proposed to play a central role in thefolding reaction and in important cell functions, and to be related to the onset ofmisfolding diseases. Due to its inherent intractability to high-resolution studies,atomistic structural models have not yet been obtained. We present here an inte-grative atomistic model of the MG formedat acidic pH by the apoflavodoxin fromthe human pathogenHelicobacter pylori. This MG has been previously shown toexhibit the archetypical expansion, spectroscopic and thermodynamic features of amolten conformation. To obtain the model, we have analyzed the stability of wild-type and 55 apoflavodoxin mutants to derive experimental equilibriumΦvaluesthat have been used in biased molecular dynamics simulations to convert thenative conformation into an MG ensemble. The ensemble has been refined toreproduce the experimental hydrodynamic radius and circular dichroism(CD) spectrum. The refined ensemble, deposited in PDB-Dev, successfully explainsthe characteristic1H-nuclear magnetic resonance (NMR) and near-UV CD spectralfeatures of the MG as well as its solvent-accessible surface area (SASA) changeupon unfolding. This integrative model of an MG will help to understand the ener-getics and roles of these elusive conformationsinproteinfoldingandmisfolding.Interestingly, the apoflavodoxin MG isstructurally unrelated to previouslydescribed partly unfolded conformations ofthis protein, exemplifying that equilib-rium MGs need not to reflect the properties of kinetic intermediates info:eu-repo/grantAgreement/ES/DGA/E45-20R info:eu-repo/grantAgreement/ES/MICINN/PDC2021-121341-I00 info:eu-repo/grantAgreement/ES/MICINN/PID2019-107293GB-I00 info:eu-repo/semantics/openAccess by-nc-nd http://creativecommons.org/licenses/by-nc-nd/3.0/es/ 8.0 2022 BIOCHEMISTRY & MOLECULAR BIOLOGY 36 / 285 = 0.126 2022 Q1 T1 4.007 2022 Biochemistry 2022 Q1 Molecular Biology 2022 Q1 Medicine (miscellaneous) 2022 Q1 10.8 2022 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Torreblanca, Renzo García-Cebollada, Helena Universidad de Zaragoza (orcid)0000-0002-9590-7371 Sancho, Javier Universidad de Zaragoza (orcid)0000-0002-2879-9200 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 31, 11 (2022), e4445 [22 pp.] Protein sci. Protein science 0961-8368 3375564 http://zaguan.unizar.es/record/120024/files/texto_completo.pdf Versión publicada 2409527 http://zaguan.unizar.es/record/120024/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:120024 articulos driver 2024-03-18-14:25:39 ARTICLE