Artificial Intracellular Filaments
Summary: Intracellular protein filaments are ubiquitous for cellular functions, but forming bona fide biomimetic intracellular filaments of small molecules in living cells remains elusive. Here, we report the in situ formation of self-limiting intracellular filaments of a small peptide via enzymatic...
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doaj-267b5605142f4457b4004f3a6c5545572020-11-25T04:01:36ZengElsevierCell Reports Physical Science2666-38642020-07-0117100085Artificial Intracellular FilamentsZhaoqianqi Feng0Huaimin Wang1Fengbin Wang2Younghoon Oh3Cristina Berciu4Qiang Cui5Edward H. Egelman6Bing Xu7Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA 02454, USADepartment of Chemistry, Brandeis University, 415 South Street, Waltham, MA 02454, USADepartment of Biochemistry and Molecular Genetics, University of Virginia, Box 800733, Charlottesville, VA 22908-0733, USADepartment of Chemistry, Boston University, 590 Commonwealth Avenue, Boston, MA 02215, USA; Rafik B. Hariri Institute for Computing and Computational Science & Engineering, Boston University, 111 Cummington Mall, Boston, MA 02215, USA; Department of Chemistry and Research Institute for Basic Science, Sogang University, Seoul 04107, Republic of KoreaMicroscopy Core Facility, McLean Hospital, Belmont, MA 02478, USADepartment of Chemistry, Boston University, 590 Commonwealth Avenue, Boston, MA 02215, USA; Corresponding authorDepartment of Biochemistry and Molecular Genetics, University of Virginia, Box 800733, Charlottesville, VA 22908-0733, USA; Corresponding authorDepartment of Chemistry, Brandeis University, 415 South Street, Waltham, MA 02454, USA; Corresponding authorSummary: Intracellular protein filaments are ubiquitous for cellular functions, but forming bona fide biomimetic intracellular filaments of small molecules in living cells remains elusive. Here, we report the in situ formation of self-limiting intracellular filaments of a small peptide via enzymatic morphological transition of a phosphorylated and trimethylated heterochiral tetrapeptide. Enzymatic dephosphorylation reduces repulsive intermolecular electrostatic interactions and converts the peptidic nanoparticles into filaments, which exhibit distinct types of cross-β structures with either C7 or C2 symmetries, with the hydrophilic C-terminal residues at the periphery of the helix. Macromolecular crowding promotes the peptide filaments to form bundles, which extend from the plasma membrane to nuclear membrane and hardly interact with endogenous components, including cytoskeletons. Stereochemistry and post-translational modification (PTM) of peptides are critical for generating the intracellular bundles. This work may offer a way to gain lost functions or to provide molecular insights for understanding normal and aberrant intracellular filaments.http://www.sciencedirect.com/science/article/pii/S2666386420300801intracellularfilamentspeptidesself-assemblycryo-EMenzyme |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhaoqianqi Feng Huaimin Wang Fengbin Wang Younghoon Oh Cristina Berciu Qiang Cui Edward H. Egelman Bing Xu |
spellingShingle |
Zhaoqianqi Feng Huaimin Wang Fengbin Wang Younghoon Oh Cristina Berciu Qiang Cui Edward H. Egelman Bing Xu Artificial Intracellular Filaments Cell Reports Physical Science intracellular filaments peptides self-assembly cryo-EM enzyme |
author_facet |
Zhaoqianqi Feng Huaimin Wang Fengbin Wang Younghoon Oh Cristina Berciu Qiang Cui Edward H. Egelman Bing Xu |
author_sort |
Zhaoqianqi Feng |
title |
Artificial Intracellular Filaments |
title_short |
Artificial Intracellular Filaments |
title_full |
Artificial Intracellular Filaments |
title_fullStr |
Artificial Intracellular Filaments |
title_full_unstemmed |
Artificial Intracellular Filaments |
title_sort |
artificial intracellular filaments |
publisher |
Elsevier |
series |
Cell Reports Physical Science |
issn |
2666-3864 |
publishDate |
2020-07-01 |
description |
Summary: Intracellular protein filaments are ubiquitous for cellular functions, but forming bona fide biomimetic intracellular filaments of small molecules in living cells remains elusive. Here, we report the in situ formation of self-limiting intracellular filaments of a small peptide via enzymatic morphological transition of a phosphorylated and trimethylated heterochiral tetrapeptide. Enzymatic dephosphorylation reduces repulsive intermolecular electrostatic interactions and converts the peptidic nanoparticles into filaments, which exhibit distinct types of cross-β structures with either C7 or C2 symmetries, with the hydrophilic C-terminal residues at the periphery of the helix. Macromolecular crowding promotes the peptide filaments to form bundles, which extend from the plasma membrane to nuclear membrane and hardly interact with endogenous components, including cytoskeletons. Stereochemistry and post-translational modification (PTM) of peptides are critical for generating the intracellular bundles. This work may offer a way to gain lost functions or to provide molecular insights for understanding normal and aberrant intracellular filaments. |
topic |
intracellular filaments peptides self-assembly cryo-EM enzyme |
url |
http://www.sciencedirect.com/science/article/pii/S2666386420300801 |
work_keys_str_mv |
AT zhaoqianqifeng artificialintracellularfilaments AT huaiminwang artificialintracellularfilaments AT fengbinwang artificialintracellularfilaments AT younghoonoh artificialintracellularfilaments AT cristinaberciu artificialintracellularfilaments AT qiangcui artificialintracellularfilaments AT edwardhegelman artificialintracellularfilaments AT bingxu artificialintracellularfilaments |
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