One-quarter of the 28 types of natural collagen exist as heterotrimers. The oligomerization state of collagen affects the structure and mechanics of the extracellular matrix, providing essential cues to modulate biological and pathological processes. A lack of high-resolution structural information limits our mechanistic understanding of collagen heterospecific self-assembly. Here, the 1.77-Å resolution structure of a synthetic heterotrimer demonstrates the balance of intermolecular electrostatics and hydrogen bonding that affects collagen stability and heterospecificity of assembly. Atomistic simulations and mutagenesis based on the solved structure are used to explore the contributions of specific interactions to energetics. A predictive model of collagen stability and specificity is developed for engineering novel collagen structures.

28种天然胶原蛋白中有四分之一以异源三聚体的形式存在。胶原蛋白的低聚状态影响细胞外基质的结构和力学，为调节生物学和病理过程提供必要的线索。缺乏高分辨率的结构信息限制了我们对胶原异种自组装的机制理解。在这里，合成异源三聚体的1.77-Å分辨率结构证明了分子间静电和氢键之间的平衡，这会影响胶原蛋白的稳定性和装配的异质性。基于解决的结构的原子模拟和诱变被用于探索特定相互作用对高能学的贡献。建立了胶原稳定性和特异性的预测模型，用于工程化新型胶原结构。