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Biophys J. 2018 Apr 24;114(8):1889-1894. doi: 10.1016/j.bpj.2018.03.017.

How Robust Is the Mechanism of Folding-Upon-Binding for an Intrinsically Disordered Protein?

Author information

1
Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Scienze Biochimiche "A. Rossi Fanelli," Istituto di Biologia e Patologia Molecolari del CNR, Sapienza Università di Roma, Rome, Italy.
2
Architecture et Fonction des Macromolécules Biologiques, UMR 7257, National Centre for Scientific Research, Aix-Marseille Université, Marseille, France.
3
Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Scienze Biochimiche "A. Rossi Fanelli," Istituto di Biologia e Patologia Molecolari del CNR, Sapienza Università di Roma, Rome, Italy. Electronic address: stefano.gianni@uniroma1.it.

Abstract

The mechanism of interaction of an intrinsically disordered protein (IDP) with its physiological partner is characterized by a disorder-to-order transition in which a recognition and a binding step take place. Even if the mechanism is quite complex, IDPs tend to bind their partner in a cooperative manner such that it is generally possible to detect experimentally only the disordered unbound state and the structured complex. The interaction between the disordered C-terminal domain of the measles virus nucleoprotein (NTAIL) and the X domain (XD) of the viral phosphoprotein allows us to detect and quantify the two distinct steps of the overall reaction. Here, we analyze the robustness of the folding of NTAIL upon binding to XD by measuring the effect on both the folding and binding steps of NTAIL when the structure of XD is modified. Because it has been shown that wild-type XD is structurally heterogeneous, populating an on-pathway intermediate under native conditions, we investigated the binding to 11 different site-directed variants of NTAIL of one particular variant of XD (I504A XD) that populates only the native state. Data reveal that the recognition and the folding steps are both affected by the structure of XD, indicating a highly malleable pathway. The experimental results are briefly discussed in the light of previous experiments on other IDPs.

PMID:
29694866
PMCID:
PMC5937165
DOI:
10.1016/j.bpj.2018.03.017
[Indexed for MEDLINE]
Free PMC Article

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