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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Main Authors: Zhaoqianqi Feng, Huaimin Wang, Fengbin Wang, Younghoon Oh, Cristina Berciu, Qiang Cui, Edward H. Egelman, Bing Xu
Format: Article
Language:English
Published: Elsevier 2020-07-01
Series:Cell Reports Physical Science
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2666386420300801
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spelling 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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