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Relevance
Silk fibers from Bombyx mori (silkworm) have been utilized by mankind since ancient times due to their remarkable mechanical properties and comfort when woven into fabrics, with the earliest records dating to around 2700 BC [3]. They are thermally comfortable, elastic, strong, and soft—properties that make silk highly sought after as a luxury fabric for garments. Silk is also biocompatible, making it applicable as a medical biomaterial for sutures, drug delivery systems, and scaffolds, where it plays a vital role in tissue regeneration[4].
Fibroins are remarkable structural proteins found across various organisms, primarily silkworms, spiders, and other arthropods, where they play critical roles in survival and ecological interactions. Bombyx mori silkworms naturally use their silk to construct a cocoon at the end of the final stage of larval development before cocoon formation, before they undergo metamorphosis into a moth. During the natural spinning process, the silkworm extrudes the silk dope (,a water-soluble liquid crystalline state containing up to 30%wt/vol fibroin in water), from its spinnerets into the external environment. This process involves mechanical shearing, stretching, and water evaporation. The delicate gland conditions (silk dope acidification, concentration changes of metal ions, and water content reduction) are crucial for the proper folding of fibroin into micelles and then liquid crystals.
Fibroins are fibrous structural proteins composed of multiple subunits that assemble into high-strength materials like silk and byssal threads. The exact subunits vary by organism, but they generally include core fibroin proteins, glycoproteins, and regulatory elements. Also some fibroins have heavy chains while other much lighter chains. Disulfide bonds play an essential role in binding glycoproteins to he heavy and light chains.
Silk fibroin transitions between two key structural states: Silk I, the soluble pre-spun form stored in silk glands, consists of type II β-turns that prevent premature crystallization, while Silk II, the spun fiber's insoluble crystalline form, is dominated by mechanically robust antiparallel β-sheets. The N-terminal domain of fibroin plays a critical regulatory role—its pH-sensitive structure (rich in acidic residues) helps maintain Silk I's solubility in the gland but triggers the shift to Silk II during spinning by undergoing conformational changes that nucleate β-sheet formation. This pH-driven mechanism, combined with shear forces and dehydration, ensures the precise, irreversible transition from Silk I's storage form to Silk II's functional fiber, optimizing silk's strength and biological utility.
Function
Basic structure
The N-terminal domain of the fibroin heavy chain (FibNT 3UA0) is a homo-tetramer composed of 268 residues, most of which are hydrophilic ( and ). FibNT's is a homodimer with eight alternating β- and a disordered (Gly109-Ser126). Its (A and B) are nearly identical except for the (Phe26-Val35):
- Chain A: Adopts a loop conformation.
- Chain B: Forms a short α-helix.
The FibNT homodimer exhibits the following : β1A–β2A–β4B–β3B–β3A–β4A–β2B–β1B, where there are two β-hairpins (Thr36–Asn65 and Glu78–Ser107) connected with two type I β-turns (Asp49–Gly52 and Asp89–Gly92). The entire assembly is stabilized by an extensive network of between adjacent β-strands.
pH-Dependent Structural Transition
The structure of fibroin is highly pH-dependent. During the natural silk-spinning process, the fibroin solution experiences a steep pH gradient along the silk gland (from anterior to posterior), which triggers the gelation of condensed fibroin. Specifically, the N-terminal domain (FibNT) remains in a disordered random-coil state at neutral pH, preventing premature β-sheet formation. Only when the pH drops to approximately 6.0 does FibNT undergo a cooperative structural transition, adopting the stable β-sheet conformation essential for fiber assembly.
Interactions between acidic residues in FibNT are critical for pH-sensitive behavior. Near the transition point (pH ~6.0), some residues exhibit up-shifted pKa values, allowing them to remain ionized at neutral pH. This sustained negative charge creates electrostatic repulsion, actively preventing premature folding and β-sheet assembly. For example, at higher pH, —such as those between Glu56–Asp44 and Asp100–Glu98—are disrupted, destabilizing β-sheet conformations until protonation occurs at lower pH.
