N-terminal Domain of TDP43 Enhances Liquid-Liquid Phase Separation of Globular Proteins
| Autor: | G. Campbell Carter, Chia Heng Hsiung, Leman Simpson, Xin Zhang, Haopeng Yang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Globular protein Recombinant Fusion Proteins Genetic Vectors Gene Expression Model system RNA-binding protein Article 03 medical and health sciences 0302 clinical medicine Coumarins Structural Biology Phase (matter) Humans Liquid liquid Protein Interaction Domains and Motifs Molecular Biology Cellular proteins Fluorescent Dyes 030304 developmental biology chemistry.chemical_classification 0303 health sciences Binding Sites Staining and Labeling Rhodamines Chemistry Fluoresceins DNA-Binding Proteins Intrinsically Disordered Proteins HEK293 Cells Biophysics Protein Multimerization 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | J Mol Biol |
| ISSN: | 0022-2836 |
| DOI: | 10.1016/j.jmb.2021.166948 |
| Popis: | Liquid-liquid phase separation (LLPS) of proteins is involved in a growing number of cellular processes. Most proteins with LLPS harbor intrinsically disordered regions (IDR), which serve as a guideline to search for cellular proteins that potentially phase separate. Herein, we reveal that oligomerization lowers the barriers for LLPS and could act as a general mechanism to enhance LLPS of proteins domains independent of IDR. Using TDP43 as a model system, we found that deleting its IDR resulted in LLPS that was dependent on the oligomerization of the N-terminal domain (NTD). Replacing TDP43's NTD with other oligomerization domains enhanced the LLPS proportionately to the state of oligomerization. In addition to TDP43, fusing NTD to other globular proteins without known LLPS behavior also drove their phase separation in a manner dependent on oligomerization. Finally, we demonstrate that heterooligomers composed of NTD-fused proteins can be driven into droplets through NTD interactions. Our results potentiate a new paradigm for using oligomerization domains as a signature to systematically identify cellular proteins with LLPS behavior, thus broadening the scope of this exciting research field. |
| Databáze: | OpenAIRE |
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