000120024 001__ 120024
000120024 005__ 20240319081004.0
000120024 0247_ $$2doi$$a10.1002/pro.4445
000120024 0248_ $$2sideral$$a130822
000120024 037__ $$aART-2022-130822
000120024 041__ $$aeng
000120024 100__ $$0(orcid)0000-0002-1896-7805$$aGalano-Frutos, Juan José$$uUniversidad de Zaragoza
000120024 245__ $$aA 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>
000120024 260__ $$c2022
000120024 5060_ $$aAccess copy available to the general public$$fUnrestricted
000120024 5203_ $$aMolten 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
000120024 536__ $$9info:eu-repo/grantAgreement/ES/DGA/E45-20R$$9info:eu-repo/grantAgreement/ES/MICINN/PDC2021-121341-I00$$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-107293GB-I00
000120024 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000120024 590__ $$a8.0$$b2022
000120024 592__ $$a4.007$$b2022
000120024 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b36 / 285 = 0.126$$c2022$$dQ1$$eT1
000120024 593__ $$aBiochemistry$$c2022$$dQ1
000120024 593__ $$aMolecular Biology$$c2022$$dQ1
000120024 593__ $$aMedicine (miscellaneous)$$c2022$$dQ1
000120024 594__ $$a10.8$$b2022
000120024 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000120024 700__ $$aTorreblanca, Renzo
000120024 700__ $$0(orcid)0000-0002-9590-7371$$aGarcía-Cebollada, Helena$$uUniversidad de Zaragoza
000120024 700__ $$0(orcid)0000-0002-2879-9200$$aSancho, Javier$$uUniversidad de Zaragoza
000120024 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000120024 773__ $$g31, 11 (2022), e4445 [22 pp.]$$pProtein sci.$$tProtein science$$x0961-8368
000120024 8564_ $$s3375564$$uhttps://zaguan.unizar.es/record/120024/files/texto_completo.pdf$$yVersión publicada
000120024 8564_ $$s2409527$$uhttps://zaguan.unizar.es/record/120024/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000120024 909CO $$ooai:zaguan.unizar.es:120024$$particulos$$pdriver
000120024 951__ $$a2024-03-18-14:25:39
000120024 980__ $$aARTICLE