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Unusual pK(a) Values Mediate the Self-Assembly of Spider Dragline Silk Proteins
[Image: see text] Spider dragline silk is a remarkably tough biomaterial and composed primarily of spidroins MaSp1 and MaSp2. During fiber self-assembly, the spidroin N-terminal domains (NTDs) undergo rapid dimerization in response to a pH gradient. However, obtaining a detailed understanding of thi...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10091414/ https://www.ncbi.nlm.nih.gov/pubmed/36990448 http://dx.doi.org/10.1021/acs.biomac.2c01344 |
Sumario: | [Image: see text] Spider dragline silk is a remarkably tough biomaterial and composed primarily of spidroins MaSp1 and MaSp2. During fiber self-assembly, the spidroin N-terminal domains (NTDs) undergo rapid dimerization in response to a pH gradient. However, obtaining a detailed understanding of this mechanism has been hampered by a lack of direct evidence regarding the protonation states of key ionic residues. Here, we elucidated the solution structures of MaSp1 and MaSp2 NTDs from Trichonephila clavipes and determined the experimental pKa values of conserved residues involved in dimerization using NMR. Surprisingly, we found that the Asp40 located on an acidic cluster protonates at an unusually high pH (∼6.5–7.1), suggesting the first step in the pH response. Then, protonation of Glu119 and Glu79 follows, with pK(a)s above their intrinsic values, contributing toward stable dimer formation. We propose that exploiting the atypical pK(a) values is a strategy to achieve tight spatiotemporal control of spider silk self-assembly. |
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