How Do We Study the Dynamic Structure of Unstructured Proteins: A Case Study on Nopp140 As an Example of a Large, Intrinsically Disordered Protein

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2018 Feb 1

PMID 29382046

Citations 16

Authors

Jung-Hyun Na

Won-Kyu Lee

Yeon Gyu Yu

Affiliations

Soon will be listed here.

Abstract

Intrinsically disordered proteins (IDPs) represent approximately 30% of the human genome and play key roles in cell proliferation and cellular signaling by modulating the function of target proteins via protein-protein interactions. In addition, IDPs are involved in various human disorders, such as cancer, neurodegenerative diseases, and amyloidosis. To understand the underlying molecular mechanism of IDPs, it is important to study their structural features during their interactions with target proteins. However, conventional biochemical and biophysical methods for analyzing proteins, such as X-ray crystallography, have difficulty in characterizing the features of IDPs because they lack an ordered three-dimensional structure. Here, we present biochemical and biophysical studies on nucleolar phosphoprotein 140 (Nopp140), which mostly consists of disordered regions, during its interaction with casein kinase 2 (CK2), which plays a central role in cell growth. Surface plasmon resonance and electron paramagnetic resonance studies were performed to characterize the interaction between Nopp140 and CK2. A single-molecule fluorescence resonance energy transfer study revealed conformational change in Nopp140 during its interaction with CK2. These studies on Nopp140 can provide a good model system for understanding the molecular function of IDPs.

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References

Lee W, Son S, Jin B, Na J, Kim S, Kim K . Structural and functional insights into the regulation mechanism of CK2 by IP6 and the intrinsically disordered protein Nopp140. Proc Natl Acad Sci U S A. 2013; 110(48):19360-5. PMC: 3845154. DOI: 10.1073/pnas.1304670110. View

Lee W, Lee S, Kim W, Rho Y, Bae Y, Lee C . Characterization of the InsP6-dependent interaction between CK2 and Nopp140. Biochem Biophys Res Commun. 2008; 376(2):439-44. DOI: 10.1016/j.bbrc.2008.09.008. View

Isaac C, Yang Y, Meier U . Nopp140 functions as a molecular link between the nucleolus and the coiled bodies. J Cell Biol. 1998; 142(2):319-29. PMC: 2133063. DOI: 10.1083/jcb.142.2.319. View

Dosztanyi Z, Meszaros B, Simon I . Bioinformatical approaches to characterize intrinsically disordered/unstructured proteins. Brief Bioinform. 2009; 11(2):225-43. DOI: 10.1093/bib/bbp061. View

Eliezer D . Biophysical characterization of intrinsically disordered proteins. Curr Opin Struct Biol. 2009; 19(1):23-30. PMC: 2728036. DOI: 10.1016/j.sbi.2008.12.004. View

Kim D, Lee C, Lee S, Kim K, Han J, Cha E . The Mechanism of p53 Rescue by SUSP4. Angew Chem Int Ed Engl. 2016; 56(5):1278-1282. DOI: 10.1002/anie.201607819. View

Ferreon A, Gambin Y, Lemke E, Deniz A . Interplay of alpha-synuclein binding and conformational switching probed by single-molecule fluorescence. Proc Natl Acad Sci U S A. 2009; 106(14):5645-50. PMC: 2667048. DOI: 10.1073/pnas.0809232106. View

Meier U, Blobel G . A nuclear localization signal binding protein in the nucleolus. J Cell Biol. 1990; 111(6 Pt 1):2235-45. PMC: 2116428. DOI: 10.1083/jcb.111.6.2235. View

Keller D, Zeng X, Wang Y, Zhang Q, Kapoor M, Shu H . A DNA damage-induced p53 serine 392 kinase complex contains CK2, hSpt16, and SSRP1. Mol Cell. 2001; 7(2):283-92. DOI: 10.1016/s1097-2765(01)00176-9. View

10.

Kim D, Wright A, Han K . An NMR study on the intrinsically disordered core transactivation domain of human glucocorticoid receptor. BMB Rep. 2017; 50(10):522-527. PMC: 5683822. DOI: 10.5483/bmbrep.2017.50.10.152. View

11.

Chemes L, Alonso L, Noval M, de Prat-Gay G . Circular dichroism techniques for the analysis of intrinsically disordered proteins and domains. Methods Mol Biol. 2012; 895:387-404. DOI: 10.1007/978-1-61779-927-3_22. View

12.

Meier U, Blobel G . NAP57, a mammalian nucleolar protein with a putative homolog in yeast and bacteria. J Cell Biol. 1994; 127(6 Pt 1):1505-14. PMC: 2120319. DOI: 10.1083/jcb.127.6.1505. View

13.

Lin A, Frost J, Deng T, Smeal T, Kikkawa U, Hunter T . Casein kinase II is a negative regulator of c-Jun DNA binding and AP-1 activity. Cell. 1992; 70(5):777-89. DOI: 10.1016/0092-8674(92)90311-y. View

14.

Dunker A, Obradovic Z, Romero P, Garner E, Brown C . Intrinsic protein disorder in complete genomes. Genome Inform Ser Workshop Genome Inform. 2001; 11:161-71. View

15.

Tawfic S, Yu S, Wang H, Faust R, Davis A, Ahmed K . Protein kinase CK2 signal in neoplasia. Histol Histopathol. 2001; 16(2):573-82. DOI: 10.14670/HH-16.573. View

16.

Drescher M, Godschalk F, Veldhuis G, van Rooijen B, Subramaniam V, Huber M . Spin-label EPR on alpha-synuclein reveals differences in the membrane binding affinity of the two antiparallel helices. Chembiochem. 2008; 9(15):2411-6. DOI: 10.1002/cbic.200800238. View

17.

Kim Y, Lee W, Jin Y, Lee K, Jeon H, Yu Y . Doxorubicin binds to un-phosphorylated form of hNopp140 and reduces protein kinase CK2-dependent phosphorylation of hNopp140. J Biochem Mol Biol. 2006; 39(6):774-81. DOI: 10.5483/bmbrep.2006.39.6.774. View

18.

Kussie P, Gorina S, Marechal V, Elenbaas B, Moreau J, Levine A . Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science. 1996; 274(5289):948-53. DOI: 10.1126/science.274.5289.948. View

19.

Yang Y, Isaac C, Wang C, Dragon F, Pogacic V, Meier U . Conserved composition of mammalian box H/ACA and box C/D small nucleolar ribonucleoprotein particles and their interaction with the common factor Nopp140. Mol Biol Cell. 2000; 11(2):567-77. PMC: 14794. DOI: 10.1091/mbc.11.2.567. View

20.

Dunker A, LAWSON J, Brown C, Williams R, Romero P, Oh J . Intrinsically disordered protein. J Mol Graph Model. 2001; 19(1):26-59. DOI: 10.1016/s1093-3263(00)00138-8. View