TY  - JOUR
A1  - Heiby, Julia C.
A1  - Goretzki, Benedikt
A1  - Johnson, Christopher M.
A1  - Hellmich, Ute
A1  - Neuweiler, Hannes
T1  - Methionine in a protein hydrophobic core drives tight interactions required for assembly of spider silk
T2  - Nature Communications
N2  - 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.
KW  - Circular dichroism
KW  - Fluorescence spectroscopy
KW  - Protein folding
KW  - Solution-state NMR
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/51278
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-512788
SN  - 2041-1723
N1  - Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
VL  - 10
IS  - 1, Art. 4378
SP  - 1
EP  - 14
PB  - Nature Publishing Group UK
CY  - [London]
ER  -