Phosphatases
SHP2 is a protein tyrosine phosphatase that dephosphorylates specific phospotyrosine residues on target proteins, most notably those of the Ras/MAPK/ERK pathway and thus plays an important role in regulating cell proliferation, differenciation, migration, division and survival. Our long-standing collaborators at the Neel Shah lab at Columbia University have developed a variety of high-throughput saturation mutagenesis platforms to characterize the functional effects of thousands of variants of SHP2. We have used molecular dynamics simulations (on the order of several tens of microseconds) to understand how these mutational variants affect the intra-protein interaction profile and dynamics of SHP2 in comparison to the wildtype protein and thus affect function. Our results have been published in a series of publications.
Membrane Microdomains
Coming soon!
Publications
-
A. E. van Vlimmeren, Z. Jiang, D. Karandur, A.T. Applebaum Licht, N. H. Shah, The pathogenic E139D mutation stabilizes a non-canonical active state of the multi-domain phosphatase SHP2, Protein Sci, 2025, 34(12), e70373 link
-
Z. Jiang, A. E. van Vlimmeren, D. Karandur, A. Semmelman, N. H. Shah, Deep mutational scanning of a multi-domain signaling protein reveals mechanisms of regulation and pathogenicity, Nature Communications, 2025, 16(1), 5464 link
-
A. E. van Vlimmeren, R. Voleti, C. A. Chartier, Z. Jiang, D. Karandur, N. H. Shah, The pathogenic T42A mutation in SHP2 rewires interaction specificity and enhances signaling, Proc. Natl. Acad. Sci. USA, 2024, 121 (30), e2407159122 link