7N57

Crystal structure of R20A human Galectin-7 mutant in presence of lactose

7N57 の概要

• エントリーDOI: 10.2210/pdb7n57/pdb
• 関連するBIRD辞書のPRD_ID: PRD_900008
• 分子名称: Galectin-7, beta-D-galactopyranose-(1-4)-alpha-D-glucopyranose, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: human galectin-7, dimer interface mutant, sugar binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 30722.36

構造登録者

Pham, N.T.H.,Calmettes, C.,Doucet, N. (登録日: 2021-06-04, 公開日: 2023-01-25, 最終更新日: 2026-03-04)

主引用文献

Pham, N.T.H.,Pare, A.,Letourneau, M.,Fortier, M.,Chatenet, D.,St-Pierre, Y.,Lague, P.,Calmettes, C.,Doucet, N.
Network-based allosteric analysis of galectin-7: Key residues dictate functional communication and stability.
Protein Sci., 35:e70502-e70502, 2026

PubMed 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. Biophysical and structural analyses confirmed that disrupting the R20-D103 interaction weakens interprotomer communication and destabilizes the dimer, while compensatory edges partially restore connectivity. These results demonstrate that residue-network fingerprinting enables predictive mapping of global communication pathways and reveal R20, R22, and D103 as key allosteric determinants of GAL-7 function. The integrative framework introduced here can be extended to identify and exploit allosteric communication pathways in other homodimeric proteins, offering a generalizable strategy for rational modulator design.

PubMed: 41700699
DOI: 10.1002/pro.70502

実験手法

X-RAY DIFFRACTION (1.83 Å)