Decoding Allostery: How Interactions Lock S100B Conformations and What K55A Mutation Teaches Us
Year: 2025
Type: article
Abstract: Allostery, also called action at a distance and ubiquitous in biological systems, is so important that it is also hailed as “the second secret of life.” In certain proteins, instead of conformational changes, proteins exhibit “dynamic” allostery. S100B is a Ca 2+ binding protein, where TRTK binding enhances Ca 2+ binding at a site 25 Å away from the metalation site and serves as a model to study “dynamic” allostery. Previous studies indicated that TRTK “blocked” both inter- and intra-subunit electrostatic and hydrophobic interactions within S100B dimeric complex, which could contribute to enhanced EFII Ca 2+ -binding affinity. To explore this further, mutagenesis of participating interacting residues (K55A) was carried out to study its conformational and thermodynamic properties using NMR experiments. We performed molecular dynamics (MD) simulations on the K55A mutant of S100B/Ca 2+ with/without TRTK. We utilized tools from network science to quantify the information transmission in these systems. The MD data suggest that in the absence of ligand, the pliable inter/intra-subunit interactions get broken in K55A to enhance Ca 2+ -binding affinity. NMR measurements provide additional evidence to support the predictions from MD simulations.
Language: English
Topic: S100 Proteins and Annexins
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Award: G6052538880
OpenAlex ID: W4416454690