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Title: | DESIGN OF PEPTIDES TO PREVENT ACTIN POLYMERIZATION | Authors: | CLEMENT PIERRE MARCEL SCIPION | ORCID iD: | orcid.org/0000-0002-3753-8475 | Keywords: | actin, md, polymerization, peptide, severing, gelsolin | Issue Date: | 18-Jan-2019 | Citation: | CLEMENT PIERRE MARCEL SCIPION (2019-01-18). DESIGN OF PEPTIDES TO PREVENT ACTIN POLYMERIZATION. ScholarBank@NUS Repository. | Abstract: | When a sizable amount of cells die at the same time, their content, which is enclosing F-actin, is released into the blood circulation, and the “actin-scavenger” system is overwhelmed. In this project, we constructed an actin-severing and sequestering peptide to supplement gelsolin in such occurrences. A WH2-motif peptide was used as a scaffold and optimized using X-ray crystallography and biochemical assays. The final peptide is able to sequester efficiently monomeric actin and sever filaments. This actin-severing peptide gives an insight on the mechanism of actin severing. In parallel, molecular dynamics simulations were used to study the behaviour of cation binding sites found in published crystal structures, as well as the cumulative probability of an activated hydrolytic water molecule approaching the γ-phosphorous of ATP in G- and F-actin. these data extend the possible roles of magnesium ions in polymerization and the mechanism of polymerization induced activation of actin’s ATPase activity. | URI: | https://scholarbank.nus.edu.sg/handle/10635/153082 |
Appears in Collections: | Ph.D Theses (Open) |
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