Molecular Recognition and Immunopharmacological Implications of Serratiopeptidase Targeting Snake Venom Bradykinin-Potentiating Peptides

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  Molecular Recognition and Immunopharmacological Implications of Serratiopeptidase Targeting Snake Venom Bradykinin-Potentiating Peptides Abstract Purpose Bradykinin-potentiating peptides (BPPs), found in snake venom, are known to modulate cardiovascular functions, but their susceptibility to enzymatic degradation remains poorly understood. Methods Models were generated using AlphaFold-Colab for five small BPPs (< 9 amino acids) that did not have experimentally solved structures, and those BPPs which had reliable predictions of structure (pLDDT > 80) were used for docking studies. Protein-peptide docking experiments were done using HADDOCK for studying the interaction between wild-type (WT) and mutant serratiopeptidase with BPPs. After selecting the best complex, simulation of the complex was done using molecular dynamics (MD) simulations for 100 ns and binding energy determination using MM/PBSA analysis. For checking the mechanical stability of the protein-peptide complexes...

Spiders Use Structural Conversion of Globular Amyloidogenic Domains to Make Strong Silk Fibers

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Spiders Use Structural Conversion of Globular Amyloidogenic Domains to Make Strong Silk Fibers

Abstract

Spider silk—an environmentally friendly protein-based material—is widely recognized for its extraordinary mechanical properties. Biomimetic spider silk-like fibers made from recombinant spider silk proteins (spidroins) currently falls short compared to natural silks in terms of mechanical performance. In this study, it is discovered that spiders use structural conversion of molecular enhancers—conserved globular 127-residue spacer domains—to make strong silk fibers. This domain lacks poly-Ala motifs but interestingly contains motifs that are similar to human amyloidogenic motifs, and that it self-assembles into amyloid-like fibrils through a non-nucleation-dependent pathway, likely to avoid the formation of cytotoxic intermediates. Incorporating this spacer domain into a recombinant chimeric spidroin facilitates self-assembly into silk-like fibers, increases fiber molecular homogeneity, and markedly enhances fiber mechanical strength. These findings highlight that spiders employ diverse strategies to produce silk with exceptional mechanical properties. The spacer domain offers a way to enhance the properties of recombinant spider silk-like fibers and other functional materials.

X. Qi, H. Wang, K. Wang, Y. Wang, A. Leppert, I. Iashchishyn, X. Zhong, Y. Zhou, R. Liu, A. Rising, M. Landreh, J. Johansson, G. Chen, Spiders Use Structural Conversion of Globular Amyloidogenic Domains to Make Strong Silk Fibers. Adv. Funct. Mater. 2024, 2315409. https://doi.org/10.1002/adfm.202315409