Differentiating between the sequence of structural events on alternative pathways of folding of a heterodimeric protein

UDGAONKAR, JAYANT B.; BHATTACHARJEE, RUPAM

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dc.contributor.author	BHATTACHARJEE, RUPAM	en_US
dc.contributor.author	UDGAONKAR, JAYANT B.	en_US
dc.date.accessioned	2023-04-21T09:28:52Z
dc.date.available	2023-04-21T09:28:52Z
dc.date.issued	2022-12	en_US
dc.identifier.citation	Distinguishing between competing pathways of folding of a protein, on the basis of how they differ in their progress of structure acquisition, remains an important challenge in protein folding studies. A previous study had shown that the heterodimeric protein, double chain monellin (dcMN) switches between alternative folding pathways upon a change in guanidine hydrochloride (GdnHCl) concentration. In the current study, the folding of dcMN has been characterized by the pulsed hydrogen exchange (HX) labeling methodology used in conjunction with mass spectrometry. Quantification of the extent to which folding intermediates accumulate and then disappear with time of folding at both low and high GdnHCl concentrations, where the folding pathways are known to be different, shows that the folding mechanism is describable by a triangular three-state mechanism. Structural characterization of the productive folding intermediates populated on the alternative pathways has enabled the pathways to be differentiated on the basis of the progress of structure acquisition that occurs on them. The intermediates on the two pathways differ in the extent to which the α-helix and the rest of the β-sheet have acquired structure that is protective against HX. The major difference is, however, that β2 has not acquired any protective structure in the intermediate formed on one pathway, but it has acquired significant protective structure in the intermediate formed on the alternative pathway. Hence, the sequence of structural events is different on the two alternative pathways.	en_US
dc.identifier.issn	0961-8368	en_US
dc.identifier.issn	1469-896X	en_US
dc.identifier.uri	https://doi.org/10.1002/pro.4513	en_US
dc.identifier.uri	http://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/7733
dc.description.abstract	Protein Science, 31(12).	en_US
dc.language.iso	en	en_US
dc.publisher	Wiley	en_US
dc.subject	Alternative pathways	en_US
dc.subject	Hydrogen exchange	en_US
dc.subject	Intermediate	en_US
dc.subject	Kinetics	en_US
dc.subject	Monellin	en_US
dc.subject	2022	en_US
dc.title	Differentiating between the sequence of structural events on alternative pathways of folding of a heterodimeric protein	en_US
dc.type	Article	en_US
dc.contributor.department	Dept. of Biology	en_US
dc.identifier.sourcetitle	Protein Science	en_US
dc.publication.originofpublisher	Foreign	en_US