ATP-dependent allosteric regulation of the ring-shaped group II chaperonins remains ill defined, in part because their complex oligomeric topology has limited the success of structural techniques in suggesting allosteric determinants. Further, their high sequence conservation has hindered the prediction of allosteric networks using mathematical covariation approaches. Here, we develop an information theoretic strategy that is robust to residue conservation and apply it to group II chaperonins. We identify a contiguous network of covarying residues that connects all nucleotide-binding pockets within each chaperonin ring. An interfacial residue between the networks of neighboring subunits controls positive cooperativity by communicating nucleotide occupancy within each ring. Strikingly, chaperonin allostery is tunable through single mutations at this position. Naturally occurring variants at this position that double the extent of positive cooperativity are less prevalent in nature. We propose that being less cooperative than attainable allows chaperonins to support robust folding over a wider range of metabolic conditions.

中文翻译：

---

信息理论框架揭示了II组伴侣蛋白中的可调变构网络

环状II型伴侣蛋白的ATP依赖性变构调节作用仍然不明确，部分原因是其复杂的寡聚体拓扑结构限制了结构技术在暗示变构决定簇方面的成功。此外，它们的高序列保守性阻碍了使用数学协变方法预测变构网络。在这里，我们开发了一种信息理论策略，可以有效地保护残基并将其应用于II类伴侣蛋白。我们确定了一个可变残基的连续网络，该网络连接每个分子伴侣环内的所有核苷酸结合口袋。相邻亚基网络之间的界面残基通过传达每个环内的核苷酸占有率来控制正协同性。惊人地 伴侣蛋白的变构可通过该位置的单个突变来调节。在这个位置上自然发生的变体，使正合作性的程度加倍，因此在自然界中不那么普遍。我们建议，合作性差于可达到的程度，可使伴侣蛋白在更广泛的代谢条件下支持牢固的折叠。