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Effects of protein G-quadruplex interactions on phase transitions and protein aggregation

We show that human protein Znf706 interacts specifically with stable, non-canonical nucleic acid structures known as G-quadruplexes. Znf706, though only 76 residues long, is comprised of two distinct domains, one disordered and one ordered. The disordered domain is homologous to the SERF family of p...

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Autores principales: Sahoo, Bikash R., Kocman, Vojč, Clark, Nathan, Myers, Nikhil, Deng, Xiexiong, Wong, Ee L., Yang, Harry J., Kotar, Anita, Guzman, Bryan B., Dominguez, Daniel, Plavec, Janez, Bardwell, James C.A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10542165/
https://www.ncbi.nlm.nih.gov/pubmed/37790366
http://dx.doi.org/10.1101/2023.09.21.558871
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author Sahoo, Bikash R.
Kocman, Vojč
Clark, Nathan
Myers, Nikhil
Deng, Xiexiong
Wong, Ee L.
Yang, Harry J.
Kotar, Anita
Guzman, Bryan B.
Dominguez, Daniel
Plavec, Janez
Bardwell, James C.A.
author_facet Sahoo, Bikash R.
Kocman, Vojč
Clark, Nathan
Myers, Nikhil
Deng, Xiexiong
Wong, Ee L.
Yang, Harry J.
Kotar, Anita
Guzman, Bryan B.
Dominguez, Daniel
Plavec, Janez
Bardwell, James C.A.
author_sort Sahoo, Bikash R.
collection PubMed
description We show that human protein Znf706 interacts specifically with stable, non-canonical nucleic acid structures known as G-quadruplexes. Znf706, though only 76 residues long, is comprised of two distinct domains, one disordered and one ordered. The disordered domain is homologous to the SERF family of proteins and acts to accelerate amyloid formation. The ordered domain contains a C2H2 type zinc-finger. We show that Znf706 not only accelerates amyloid formation but also accelerates amorphous protein aggregation. We find that Znf706 binds preferentially to parallel G-quadruplexes with low micromolar affinity, primarily using its N-terminus, whose dynamics are constrained upon interaction. G-quadruplexes are potent anti-aggregation agents, and their binding to Znf706 suppresses Znf706’s ability to accelerate protein aggregation and fibril formation. Znf706 in conjunction with G-quadruplexes thus may play a role in regulating protein folding. Depletion of Znf706 specifically impacts mRNA abundance of genes that contain high G-quadruplex density, implying that Znf706 may also serve as a G-quadruplex specific regulator. Our studies give insights into how proteins and G-quadruplexes interact, how these interactions affect both partners, lead to liquid-liquid phase transitions, and lead to the modulation of protein aggregation and cellular mRNA levels.
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spelling pubmed-105421652023-10-03 Effects of protein G-quadruplex interactions on phase transitions and protein aggregation Sahoo, Bikash R. Kocman, Vojč Clark, Nathan Myers, Nikhil Deng, Xiexiong Wong, Ee L. Yang, Harry J. Kotar, Anita Guzman, Bryan B. Dominguez, Daniel Plavec, Janez Bardwell, James C.A. bioRxiv Article We show that human protein Znf706 interacts specifically with stable, non-canonical nucleic acid structures known as G-quadruplexes. Znf706, though only 76 residues long, is comprised of two distinct domains, one disordered and one ordered. The disordered domain is homologous to the SERF family of proteins and acts to accelerate amyloid formation. The ordered domain contains a C2H2 type zinc-finger. We show that Znf706 not only accelerates amyloid formation but also accelerates amorphous protein aggregation. We find that Znf706 binds preferentially to parallel G-quadruplexes with low micromolar affinity, primarily using its N-terminus, whose dynamics are constrained upon interaction. G-quadruplexes are potent anti-aggregation agents, and their binding to Znf706 suppresses Znf706’s ability to accelerate protein aggregation and fibril formation. Znf706 in conjunction with G-quadruplexes thus may play a role in regulating protein folding. Depletion of Znf706 specifically impacts mRNA abundance of genes that contain high G-quadruplex density, implying that Znf706 may also serve as a G-quadruplex specific regulator. Our studies give insights into how proteins and G-quadruplexes interact, how these interactions affect both partners, lead to liquid-liquid phase transitions, and lead to the modulation of protein aggregation and cellular mRNA levels. Cold Spring Harbor Laboratory 2023-09-21 /pmc/articles/PMC10542165/ /pubmed/37790366 http://dx.doi.org/10.1101/2023.09.21.558871 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Sahoo, Bikash R.
Kocman, Vojč
Clark, Nathan
Myers, Nikhil
Deng, Xiexiong
Wong, Ee L.
Yang, Harry J.
Kotar, Anita
Guzman, Bryan B.
Dominguez, Daniel
Plavec, Janez
Bardwell, James C.A.
Effects of protein G-quadruplex interactions on phase transitions and protein aggregation
title Effects of protein G-quadruplex interactions on phase transitions and protein aggregation
title_full Effects of protein G-quadruplex interactions on phase transitions and protein aggregation
title_fullStr Effects of protein G-quadruplex interactions on phase transitions and protein aggregation
title_full_unstemmed Effects of protein G-quadruplex interactions on phase transitions and protein aggregation
title_short Effects of protein G-quadruplex interactions on phase transitions and protein aggregation
title_sort effects of protein g-quadruplex interactions on phase transitions and protein aggregation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10542165/
https://www.ncbi.nlm.nih.gov/pubmed/37790366
http://dx.doi.org/10.1101/2023.09.21.558871
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