How Intrinsically Disordered Proteins Modulate Biomolecular Condensates

被引:1
作者
Wang, Yanyan [1 ]
Chen, Limin [1 ]
Li, Siyang [1 ]
Lai, Luhua [1 ]
机构
[1] Peking Univ, Acad Adv Interdisplinary Studies, Chinese Acad Med Sci 2021RU014, Coll Chem & Mol Engn,Unit Drug Design Method, Beijing 100871, Peoples R China
关键词
intrinsically disordered proteins; biomolecular codensates; driving force; chemical compound regulation; LIQUID PHASE-SEPARATION; FORCE-FIELD; DOMAIN; PHOSPHORYLATION; GRANULES; MECHANISMS; POLYMERS; DROPLETS; BINDING; VIEW;
D O I
10.7535/PC220324
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Biomolecular condensates form various cellular membraneless organelles and play diverse biological functions as a result of their specific physicochemical properties. For example, biomolecular condensates are able to perceive changes in the external environment, regulate the cellular concentration of proteins, modulate different signaling pathways and selectively partition hub protiens as well as nucleic acids. Abnormal formation and changes of biomolecular condensates are closely related to human diseases, especially neurodegenerative diseases, cancers and viral diseases such as COVID-19. Intrinsically disordered proteins (IDPs) play key roles in the formation and regulation of biomolecular condensates formation and regulation, propose the possibility of rationally regulating biomolecular condensates through ligand design targeting IDPs, and discuss the challenges of understanding biomolecular condensates through ligand design targeting IDPs, and discuss the challenges of understanding biomolecular condensate formation and regulation mechanisms and for discovering novel chemical compounds to modulate biomolecular condensates.
引用
收藏
页码:1610 / 1618
页数:9
相关论文
共 93 条
[1]   Liquid-liquid phase separation of the microtubule-binding repeats of the Alzheimer-related protein Tau [J].
Ambadipudi, Susmitha ;
Biernat, Jacek ;
Riedel, Dietmar ;
Mandelkow, Eckhard ;
Zweckstetter, Markus .
NATURE COMMUNICATIONS, 2017, 8
[2]   Stress granules: The Tao of RNA triage [J].
Anderson, Paul ;
Kedersha, Nancy .
TRENDS IN BIOCHEMICAL SCIENCES, 2008, 33 (03) :141-150
[3]  
Aumiller WM, 2016, NAT CHEM, V8, P129, DOI [10.1038/nchem.2414, 10.1038/NCHEM.2414]
[4]   Biomolecular condensates: organizers of cellular biochemistry [J].
Banani, Salman F. ;
Lee, Hyun O. ;
Hyman, Anthony A. ;
Rosen, Michael K. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2017, 18 (05) :285-298
[5]   Small-molecule antagonists of Myc/Max dimerization inhibit Myc-induced transformation of chicken embryo fibroblasts [J].
Berg, T ;
Cohen, SB ;
Desharnais, J ;
Sonderegger, C ;
Maslyar, DJ ;
Goldberg, J ;
Boger, DL ;
Vogt, PK .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (06) :3830-3835
[6]   Finding Our Way in the Dark Proteome [J].
Bhowmick, Asmit ;
Brookes, David H. ;
Yost, Shane R. ;
Dyson, H. Jane ;
Forman-Kay, Julie D. ;
Gunter, Daniel ;
Head-Gordon, Martin ;
Hura, Gregory L. ;
Pande, Vijay S. ;
Wemmer, David E. ;
Wright, Peter E. ;
Head-Gordon, Teresa .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2016, 138 (31) :9730-9742
[7]   Intrinsically disordered proteins and biomolecular condensates as drug targets [J].
Biesaga, Mateusz ;
Frigole-Vivas, Marta ;
Salvatella, Xavier .
CURRENT OPINION IN CHEMICAL BIOLOGY, 2021, 62 :90-100
[8]   Biomolecular Condensates and Cancer [J].
Boija, Ann ;
Klein, Isaac A. ;
Young, Richard A. .
CANCER CELL, 2021, 39 (02) :174-192
[9]   Discovery of a Functional Covalent Ligand Targeting an Intrinsically Disordered Cysteine within MYC [J].
Boike, Lydia ;
Cioffi, Alexander G. ;
Majewski, Felix C. ;
Co, Jennifer ;
Henning, Nathaniel J. ;
Jones, Michael D. ;
Liu, Gang ;
McKenna, Jeffrey M. ;
Tallarico, John A. ;
Schirle, Markus ;
Nomura, Daniel K. .
CELL CHEMICAL BIOLOGY, 2021, 28 (01) :4-+
[10]   Structural and hydrodynamic properties of an intrinsically disordered region of a germ cell-specific protein on phase separation [J].
Brady, Jacob P. ;
Farber, Patrick J. ;
Sekhar, Ashok ;
Lin, Yi-Hsuan ;
Huang, Rui ;
Bah, Alaji ;
Nott, Timothy J. ;
Chan, Hue Sun ;
Baldwin, Andrew J. ;
Forman-Kay, Julie D. ;
Kay, Lewis E. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2017, 114 (39) :E8194-E8203