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Assessing the dynamics and macromolecular interactions of the intrinsically disordered protein YY1

YY1 is a ubiquitously expressed, intrinsically disordered transcription factor involved in neural development. The oligomeric state of YY1 varies depending on the environment. These structural changes may alter its DNA binding ability and hence its transcriptional activity. Just as YY1’s oligomeric...

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Autores principales: Donald, Heather, Blane, Ashleigh, Buthelezi, Sindisiwe, Naicker, Previn, Stoychev, Stoyan, Majakwara, Jacob, Fanucchi, Sylvia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10611921/
https://www.ncbi.nlm.nih.gov/pubmed/37815922
http://dx.doi.org/10.1042/BSR20231295
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author Donald, Heather
Blane, Ashleigh
Buthelezi, Sindisiwe
Naicker, Previn
Stoychev, Stoyan
Majakwara, Jacob
Fanucchi, Sylvia
author_facet Donald, Heather
Blane, Ashleigh
Buthelezi, Sindisiwe
Naicker, Previn
Stoychev, Stoyan
Majakwara, Jacob
Fanucchi, Sylvia
author_sort Donald, Heather
collection PubMed
description YY1 is a ubiquitously expressed, intrinsically disordered transcription factor involved in neural development. The oligomeric state of YY1 varies depending on the environment. These structural changes may alter its DNA binding ability and hence its transcriptional activity. Just as YY1’s oligomeric state can impact its role in transcription, so does its interaction with other proteins such as FOXP2. The aim of this work is to study the structure and dynamics of YY1 so as to determine the influence of oligomerisation and associations with FOXP2 on its DNA binding mechanism. The results confirm that YY1 is primarily a disordered protein, but it does consist of certain specific structured regions. We observed that YY1 quaternary structure is a heterogenous mixture of oligomers, the overall size of which is dependent on ionic strength. Both YY1 oligomerisation and its dynamic behaviour are further subject to changes upon DNA binding, whereby increases in DNA concentration result in a decrease in the size of YY1 oligomers. YY1 and the FOXP2 forkhead domain were found to interact with each other both in isolation and in the presence of YY1-specific DNA. The heterogeneous, dynamic multimerisation of YY1 identified in this work is, therefore likely to be important for its ability to make heterologous associations with other proteins such as FOXP2. The interactions that YY1 makes with itself, FOXP2 and DNA form part of an intricate mechanism of transcriptional regulation by YY1, which is vital for appropriate neural development.
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spelling pubmed-106119212023-10-29 Assessing the dynamics and macromolecular interactions of the intrinsically disordered protein YY1 Donald, Heather Blane, Ashleigh Buthelezi, Sindisiwe Naicker, Previn Stoychev, Stoyan Majakwara, Jacob Fanucchi, Sylvia Biosci Rep Biophysics YY1 is a ubiquitously expressed, intrinsically disordered transcription factor involved in neural development. The oligomeric state of YY1 varies depending on the environment. These structural changes may alter its DNA binding ability and hence its transcriptional activity. Just as YY1’s oligomeric state can impact its role in transcription, so does its interaction with other proteins such as FOXP2. The aim of this work is to study the structure and dynamics of YY1 so as to determine the influence of oligomerisation and associations with FOXP2 on its DNA binding mechanism. The results confirm that YY1 is primarily a disordered protein, but it does consist of certain specific structured regions. We observed that YY1 quaternary structure is a heterogenous mixture of oligomers, the overall size of which is dependent on ionic strength. Both YY1 oligomerisation and its dynamic behaviour are further subject to changes upon DNA binding, whereby increases in DNA concentration result in a decrease in the size of YY1 oligomers. YY1 and the FOXP2 forkhead domain were found to interact with each other both in isolation and in the presence of YY1-specific DNA. The heterogeneous, dynamic multimerisation of YY1 identified in this work is, therefore likely to be important for its ability to make heterologous associations with other proteins such as FOXP2. The interactions that YY1 makes with itself, FOXP2 and DNA form part of an intricate mechanism of transcriptional regulation by YY1, which is vital for appropriate neural development. Portland Press Ltd. 2023-10-27 /pmc/articles/PMC10611921/ /pubmed/37815922 http://dx.doi.org/10.1042/BSR20231295 Text en © 2023 The Author(s). https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Biophysics
Donald, Heather
Blane, Ashleigh
Buthelezi, Sindisiwe
Naicker, Previn
Stoychev, Stoyan
Majakwara, Jacob
Fanucchi, Sylvia
Assessing the dynamics and macromolecular interactions of the intrinsically disordered protein YY1
title Assessing the dynamics and macromolecular interactions of the intrinsically disordered protein YY1
title_full Assessing the dynamics and macromolecular interactions of the intrinsically disordered protein YY1
title_fullStr Assessing the dynamics and macromolecular interactions of the intrinsically disordered protein YY1
title_full_unstemmed Assessing the dynamics and macromolecular interactions of the intrinsically disordered protein YY1
title_short Assessing the dynamics and macromolecular interactions of the intrinsically disordered protein YY1
title_sort assessing the dynamics and macromolecular interactions of the intrinsically disordered protein yy1
topic Biophysics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10611921/
https://www.ncbi.nlm.nih.gov/pubmed/37815922
http://dx.doi.org/10.1042/BSR20231295
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