Bidirectional protein–protein interactions control liquid–liquid phase separation of PSD-95 and its interaction partners

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Bidirectional protein–protein interactions control liquid–liquid phase separation of PSD-95 and its interaction partners. / Christensen, Nikolaj Riis; Pedersen, Christian Parsbæk; Sereikaite, Vita; Pedersen, Jannik Nedergaard; Vistrup-Parry, Maria; Sørensen, Andreas Toft; Otzen, Daniel; Teilum, Kaare; Madsen, Kenneth Lindegaard; Strømgaard, Kristian.

In: iScience, Vol. 25, No. 2, 103808, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Christensen, NR, Pedersen, CP, Sereikaite, V, Pedersen, JN, Vistrup-Parry, M, Sørensen, AT, Otzen, D, Teilum, K, Madsen, KL & Strømgaard, K 2022, 'Bidirectional protein–protein interactions control liquid–liquid phase separation of PSD-95 and its interaction partners', iScience, vol. 25, no. 2, 103808. https://doi.org/10.1016/j.isci.2022.103808

APA

Christensen, N. R., Pedersen, C. P., Sereikaite, V., Pedersen, J. N., Vistrup-Parry, M., Sørensen, A. T., Otzen, D., Teilum, K., Madsen, K. L., & Strømgaard, K. (2022). Bidirectional protein–protein interactions control liquid–liquid phase separation of PSD-95 and its interaction partners. iScience, 25(2), [103808]. https://doi.org/10.1016/j.isci.2022.103808

Vancouver

Christensen NR, Pedersen CP, Sereikaite V, Pedersen JN, Vistrup-Parry M, Sørensen AT et al. Bidirectional protein–protein interactions control liquid–liquid phase separation of PSD-95 and its interaction partners. iScience. 2022;25(2). 103808. https://doi.org/10.1016/j.isci.2022.103808

Author

Christensen, Nikolaj Riis ; Pedersen, Christian Parsbæk ; Sereikaite, Vita ; Pedersen, Jannik Nedergaard ; Vistrup-Parry, Maria ; Sørensen, Andreas Toft ; Otzen, Daniel ; Teilum, Kaare ; Madsen, Kenneth Lindegaard ; Strømgaard, Kristian. / Bidirectional protein–protein interactions control liquid–liquid phase separation of PSD-95 and its interaction partners. In: iScience. 2022 ; Vol. 25, No. 2.

Bibtex

@article{cc8ec939c76b411bbb44df2efc49eef2,
title = "Bidirectional protein–protein interactions control liquid–liquid phase separation of PSD-95 and its interaction partners",
abstract = "The organization of the postsynaptic density (PSD), a protein-dense semi-membraneless organelle, is mediated by numerous specific protein–protein interactions (PPIs) which constitute a functional postsynapse. The PSD protein 95 (PSD-95) interacts with a manifold of proteins, including the C-terminal of transmembrane AMPA receptor (AMPAR) regulatory proteins (TARPs). Here, we uncover the minimal essential peptide responsible for the Stargazin (TARP-γ2)-mediated liquid–liquid phase separation (LLPS) formation of PSD-95 and other key protein constituents of the PSD. Furthermore, we find that pharmacological inhibitors of PSD-95 can facilitate the formation of LLPS. We found that in some cases LLPS formation is dependent on multivalent interactions, while in other cases short, highly charged peptides are sufficient to promote LLPS in complex systems. This study offers a new perspective on PSD-95 interactions and their role in LLPS formation, while also considering the role of affinity over multivalency in LLPS systems.",
keywords = "Biomolecules, Biophysics, molecular biology, molecular neuroscience, Pharmacology",
author = "Christensen, {Nikolaj Riis} and Pedersen, {Christian Parsb{\ae}k} and Vita Sereikaite and Pedersen, {Jannik Nedergaard} and Maria Vistrup-Parry and S{\o}rensen, {Andreas Toft} and Daniel Otzen and Kaare Teilum and Madsen, {Kenneth Lindegaard} and Kristian Str{\o}mgaard",
note = "Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
doi = "10.1016/j.isci.2022.103808",
language = "English",
volume = "25",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier",
number = "2",

}

RIS

TY - JOUR

T1 - Bidirectional protein–protein interactions control liquid–liquid phase separation of PSD-95 and its interaction partners

AU - Christensen, Nikolaj Riis

AU - Pedersen, Christian Parsbæk

AU - Sereikaite, Vita

AU - Pedersen, Jannik Nedergaard

AU - Vistrup-Parry, Maria

AU - Sørensen, Andreas Toft

AU - Otzen, Daniel

AU - Teilum, Kaare

AU - Madsen, Kenneth Lindegaard

AU - Strømgaard, Kristian

N1 - Publisher Copyright: © 2022 The Authors

PY - 2022

Y1 - 2022

N2 - The organization of the postsynaptic density (PSD), a protein-dense semi-membraneless organelle, is mediated by numerous specific protein–protein interactions (PPIs) which constitute a functional postsynapse. The PSD protein 95 (PSD-95) interacts with a manifold of proteins, including the C-terminal of transmembrane AMPA receptor (AMPAR) regulatory proteins (TARPs). Here, we uncover the minimal essential peptide responsible for the Stargazin (TARP-γ2)-mediated liquid–liquid phase separation (LLPS) formation of PSD-95 and other key protein constituents of the PSD. Furthermore, we find that pharmacological inhibitors of PSD-95 can facilitate the formation of LLPS. We found that in some cases LLPS formation is dependent on multivalent interactions, while in other cases short, highly charged peptides are sufficient to promote LLPS in complex systems. This study offers a new perspective on PSD-95 interactions and their role in LLPS formation, while also considering the role of affinity over multivalency in LLPS systems.

AB - The organization of the postsynaptic density (PSD), a protein-dense semi-membraneless organelle, is mediated by numerous specific protein–protein interactions (PPIs) which constitute a functional postsynapse. The PSD protein 95 (PSD-95) interacts with a manifold of proteins, including the C-terminal of transmembrane AMPA receptor (AMPAR) regulatory proteins (TARPs). Here, we uncover the minimal essential peptide responsible for the Stargazin (TARP-γ2)-mediated liquid–liquid phase separation (LLPS) formation of PSD-95 and other key protein constituents of the PSD. Furthermore, we find that pharmacological inhibitors of PSD-95 can facilitate the formation of LLPS. We found that in some cases LLPS formation is dependent on multivalent interactions, while in other cases short, highly charged peptides are sufficient to promote LLPS in complex systems. This study offers a new perspective on PSD-95 interactions and their role in LLPS formation, while also considering the role of affinity over multivalency in LLPS systems.

KW - Biomolecules

KW - Biophysics

KW - molecular biology

KW - molecular neuroscience

KW - Pharmacology

U2 - 10.1016/j.isci.2022.103808

DO - 10.1016/j.isci.2022.103808

M3 - Journal article

C2 - 35198873

AN - SCOPUS:85124178003

VL - 25

JO - iScience

JF - iScience

SN - 2589-0042

IS - 2

M1 - 103808

ER -

ID: 298239210