Pi-Pi contacts are an overlooked protein feature relevant to phase separation
By Robert M. Vernon, P. A. Chong, B. Tsang, Tae Hun Kim, Alaji Bah, P. Farber, Hong Lin, Julie D. Forman-Kay. eLife, 2018
666 citations recorded by the source corpus.
Protein phase separation is implicated in formation of membraneless organelles, signaling puncta and the nuclear pore. Multivalent interactions of modular binding domains and their target motifs can drive phase separation. However, forces promoting the more common phase separation of intrinsically disordered regions are less understood, with suggested roles for multivalent cation-pi, pi-pi, and charge interactions and the hydrophobic effect. Known phase-separating proteins are enriched in pi-orbital containing residues and thus we analyzed pi-interactions in folded proteins. We found that pi-pi interactions involving non-aromatic groups are widespread, underestimated by force-fields used in structure calculations and correlated with solvation and lack of regular secondary structure, properties associated with disordered regions. We present a phase separation predictive algorithm based on pi interaction frequency, highlighting proteins involved in biomaterials and RNA processing.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/131df03db396ed154bbf0c35a337d680378a3a62
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Molecular Biology
- Alex S. Holehouse
- Rohit V. Pappu
- J. R. Espinosa
- Rosana Collepardo-Guevara
- Adiran Garaizar
- Anne Aguirre
- Kieran O. Russell
- Ping Chew
Citations in the corpus
- Physical Principles Underlying the Complex Biology of Intracellular Phase Transitions (2020, methodology): “In contrast, we can perform a systematic mutation of specific residues of interest, identified a priori using bioinformatics approaches (122, 166, 167, 178), to all possible amino acids.”
- Physics-driven coarse-grained model for biomolecular phase separation with near-quantitative accuracy (2021, methodology): “To parameterize the non-bonded short-ranged terms described via the WF potential, we first determined the relative π – π contact frequencies for amino acids from the work of Vernon et al. 13 (Supplementary Table 1), who predicted the planar π – π contact frequencies from a survey of ~6,000 high-reso”