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RESEARCH PRODUCT
Methionine in a protein hydrophobic core drives tight interactions required for assembly of spider silk
Julia C. HeibyBenedikt GoretzkiChristopher M. JohnsonUte A. HellmichHannes Neuweilersubject
congenital hereditary and neonatal diseases and abnormalitiesProtein Foldinggenetic structuresProtein ConformationScienceSilkmacromolecular substancesCircular dichroismcomplex mixturesArticleMethionineddc:590ddc:570AnimalsAmino Acid Sequencelcsh:ScienceFluorescence spectroscopySequence Homology Amino AcidfungiQtechnology industry and agricultureSpidersSpectrometry FluorescenceMutationThermodynamicslcsh:QProtein MultimerizationFibroinsSolution-state NMRHydrophobic and Hydrophilic InteractionsAlgorithmsdescription
Web spiders connect silk proteins, so-called spidroins, into fibers of extraordinary toughness. The spidroin N-terminal domain (NTD) plays a pivotal role in this process: it polymerizes spidroins through a complex mechanism of dimerization. Here we analyze sequences of spidroin NTDs and find an unusually high content of the amino acid methionine. We simultaneously mutate all methionines present in the hydrophobic core of a spidroin NTD from a nursery web spider’s dragline silk to leucine. The mutated NTD is strongly stabilized and folds at the theoretical speed limit. The structure of the mutant is preserved, yet its ability to dimerize is substantially impaired. We find that side chains of core methionines serve to mobilize the fold, which can thereby access various conformations and adapt the association interface for tight binding. Methionine in a hydrophobic core equips a protein with the capacity to dynamically change shape and thus to optimize its function.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-09-01 | Nature Communications |