PT  - JOURNAL ARTICLE
AU  - Allen K. Kim
AU  - Takanari Inoue
TI  - Rational design of a synthetic farnesyl-electrostatic switch based on the hypervariable region of K-Ras4b
AID  - 10.1101/635839
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 635839
4099  - http://biorxiv.org/content/early/2019/05/15/635839.short
4100  - http://biorxiv.org/content/early/2019/05/15/635839.full
AB  - We rationally designed and developed a farnesyl-electrostatic switch that synthetically responds to an intended stimulus. Our design is a de novo amino acid sequence that mimics the switching behavior observed in K-Ras4b upon phosphorylation of serine-181. We built our peptide based on observations that the hypervariable region in the C-terminus of K-Ras4b contains: 1) a cluster of basic residues which electrostatically interact with the inner leaflet of the plasma membrane, 2) phosphorylation sites which will post-translationally change the positive charge content of the signaling sequence, and 3) a farnesylation recognition sequence which allows the protein to be anchored onto the cellular membrane system. We used this peptide to perform basic characterization of the farnesyl-electrostatic switch mechanism. We envision that it can have utility in future studies as a kinase sensor or as a module for perturbing signal transduction pathways.