Network-based allosteric analysis of galectin-7: Key residues dictate functional communication and stability.

ABSTRACT: Allosteric modulation enables precise control of protein activity but remains difficult to harness for selective inhibitor design. Traditional high-throughput screening for allosteric modulators is still costly and time-consuming, underscoring the need for predictive computational approaches. Here, we combined network and shortest-path analyses to predict interprotomer communication nodes that regulate the pro-apoptotic activity of human galectin-7 (GAL-7). We identify a minimal electrostatic network (R20-R22-D103) as a key allosteric node controlling dimer stability and signal transmission between the two distant glycan binding sites. Our predictions guided the engineering of four variants (R20A, R22A, D103A, and R20A-R22A), all of which impaired GAL-7-induced apoptosis in human T cells.

SUBMITTER: Pham NTH 

PROVIDER: S-EPMC12910631 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature