Identification and Structural Characterization of an Intermediate in the Folding of the Measles Virus X Domain

被引：16

作者：

Bonetti, Daniela ^{[1
,2
]}

Camilloni, Carlo ^{[3
,4
,5
]}

Visconti, Lorenzo ^{[1
,2
]}

Longhi, Sonia ^{[6
,7
]}

Brunori, Maurizio ^{[1
,2
]}

Vendruscolo, Michele ^{[3
]}

Gianni, Stefano ^{[1
,2
,3
]}

机构：

[1] Univ Roma La Sapienza, Ist Pasteur Fdn Cenci Bolognetti, I-00185 Rome, Italy

[2] Univ Roma La Sapienza, Ist Biol & Patol Mol, CNR, Dipartimento Sci Biochim A Rossi Fanelli, I-00185 Rome, Italy

[3] Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England

[4] Tech Univ Munich, Dept Chem, Lichtenbergstr 4, D-85747 Garching, Germany

[5] Tech Univ Munich, Inst Adv Study, Lichtenbergstr 4, D-85747 Garching, Germany

[6] Aix Marseille Univ, CNRS, UMR 7257, AFMB, F-13288 Marseille, France

[7] CNRS, AFMB UMR 7257, F-13288 Marseille, France

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2016年 / 291卷 / 20期

关键词：

ON-PATHWAY INTERMEDIATE; REPLICA-AVERAGED METADYNAMICS; C-TERMINAL DOMAIN; PROTEIN-STRUCTURE; KINETIC-ANALYSIS; DENATURED STATE; 3-STATE MODEL; PDZ DOMAIN; MECHANISM; BINDING;

D O I：

10.1074/jbc.M116.721126

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Although most proteins fold by populating intermediates, the transient nature of such states makes it difficult to characterize their structures. In this work we identified and characterized the structure of an intermediate of the X domain of phosphoprotein (P) of measles virus. We obtained this result by a combination of equilibrium and kinetic measurements and NMR chemical shifts used as structural restraints in replica-averaged metadynamics simulations. The structure of the intermediate was then validated by rationally designing four mutational variants predicted to affect the stability of this state. These results provide a detailed view of an intermediate state and illustrate the opportunities offered by a synergistic use of experimental and computational methods to describe non-native states at atomic resolution.

引用

页码：10886 / 10892

页数：7

共 38 条

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