Han, Kyung reem Soon Ho Kim Venable, Richard Pastor, Richard W. 2024-01-12T03:31:07Z 2024-01-12T03:31:07Z 2022-05-05 2022-05 0027-8424 https://pubs.kist.re.kr/handle/201004/76732 Phosphatidylinositol 4,5-bisphosphate (PIP2) clustering is a key component in cell signaling, yet little is known about the atomic-level features of this phenomenon. Network-theoretic analysis of multimicrosecond atomistic simulations of PIP2 containing asymmetric bilayers under protein-free conditions, presented here, reveals how design principles of PIP2 clustering are determined by the specific cation effects. Ca2+ generates large clusters (6% are pentamer or larger) by adding existing PIP2 dimers formed by strong O？Ca2+？O bridging interactions of unprotonated P4/P5 phosphates. In contrast, monovalent cations (Na+ and K+) form smaller and less-stable clusters by preferentially adding PIP2 monomers. Despite having the same net charge, the affinity to P4/P5 is higher for Na+, while affinity toward glycerol P1 is higher for K+. Consequently, a mixture of K+ and Ca2+ (as would be produced by Ca2+ influx) synergistically yields larger and more stable clusters than Ca2+ alone due to the different binding preferences of these cations. English National Academy of Sciences Design Principles of PI(4,5)P2 Clustering Under Protein-Free Conditions: Specific Cation Effects and Calcium-Potassium Synergy Article 10.1073/pnas.2202647119 1 Proceedings of the National Academy of Sciences of the United States of America, v.119, no.22, pp.e220264711 Proceedings of the National Academy of Sciences of the United States of America 119 22 e220264711 N scie scopus 001051437000015 Multidisciplinary Sciences Science & Technology - Other Topics Article CLEAVAGE FURROW PIP2 MEMBRANES PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE PHOSPHOINOSITIDES ORGANIZATION SIMULATIONS VALIDATION DYNAMICS REGIONS PI(4,5)P2 clustering specific ion effects all-atom molecular dynamics network theory