2026-02-05 英国・キングス・カレッジ・ロンドン(KCL)
＜関連情報＞
- https://www.kcl.ac.uk/news/scientists-uncover-the-molecular-marvel-behind-spider-silks-super-powers
- https://www.pnas.org/doi/10.1073/pnas.2523198122
Arg–Tyrカチオン–π相互作用が、天然のクモの牽引糸における相分離とβシート集合を促進する Arg–Tyr cation–π interactions drive phase separation and β-sheet assembly in native spider dragline silk
Hannah R. Johnson, Kevin Chalek, Nesreen Elathram, +10 , and Gregory P. Holland
Proceedings of the National Academy of Sciences Published:December 23, 2025
DOI:https://doi.org/10.1073/pnas.2523198122
Significance
Spider silk is one of nature’s toughest materials, yet how its soluble protein building blocks transform into solid fibers remains elusive. We show that interactions between specific amino acids—arginine and tyrosine—act as molecular “stickers” that connect liquid–liquid phase separation (LLPS) with structural ordering. These interactions promote condensation and persist within emerging β-sheet regions, linking molecular chemistry to macroscopic assembly. By integrating NMR spectroscopy, molecular simulations, and AI-based structural modeling, our work reveals how sequence-encoded interactions guide silk protein organization. These findings establish a framework for understanding how proteins harness phase separation to form functional materials and may inspire design principles for next-generation biomimetic fibers.
Abstract
Liquid–liquid phase separation (LLPS) is a fundamental principle of protein organization in intrinsically disordered proteins (IDPs) and biomaterials, yet the residue-level interactions that link condensation to structural ordering remain poorly defined. In spider dragline silk, LLPS is believed to initiate the transition from soluble spidroin dope into β-sheet–rich fibers that provide exceptional toughness, yet how sequence-specific motifs govern this process has been unclear. Here, we combine isotope-edited solution NMR, dynamic nuclear polarization (DNP)–enhanced solid-state NMR, molecular dynamics simulations, and AlphaFold3 modeling to define the molecular role of arginine and tyrosine in Latrodectus hesperus dragline silk. Phosphate triggers LLPS while preserving intrinsic disorder, with arginine exhibiting the largest chemical shift perturbations. Simulations reveal that phosphate displaces hydration water to promote Arg–Tyr cation–π interactions and weaken Arg–poly(Ala) contacts. Solid-state NMR directly detects Arg–Tyr contacts in spun fibers, demonstrating that arginine is partially incorporated into β-sheet interfaces while tyrosine frequently adopts β-turn conformations. AlphaFold3 models corroborate these interfacial geometries and reproduce experimental chemical shifts, supporting persistent Arg–Tyr interactions at structured–unstructured boundaries. Together, these results identify Arg–Tyr contacts as critical “sticker” interactions that mediate condensation, nucleate local order, and stabilize fiber architecture. More broadly, this work establishes a mechanistic link between residue-specific chemistry, LLPS, and hierarchical assembly in a structural protein. These insights highlight how weak multivalent interactions bridge disordered and ordered states, providing a general framework for condensate-driven assembly in biology and guiding biomimetic material design.
