ArticleProceedings of the National Academy of Sciences of the United States of America2004
Use of sequence duplication to engineer a ligand-triggered, long-distance molecular switch in T4 lysozyme.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- Seesaw protein: Design of a protein that adopts interconvertible alternative functional conformations and its dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Molecular dynamics simulations of an engineered T4 lysozyme exclude helix to sheet transition, and provide insights into long distance, intra-protein switchable motion.Protein science : a publication of the Protein Society · 2020Article
- Designing redox potential-controlled protein switches based on mutually exclusive proteins.Protein science : a publication of the Protein Society · 2012Article
- Emerging area: biomaterials that mimic and exploit protein motion.Soft matter · 2011Article
- Converting a protein into a switch for biosensing and functional regulation.Protein science : a publication of the Protein Society · 2011Review
- Beyond molecular beacons: optical sensors based on the binding-induced folding of proteins and polypeptides.Chemistry (Weinheim an der Bergstrasse, Germany) · 2009Article
- A Ca2+-sensing molecular switch based on alternate frame protein folding.ACS chemical biology · 2008Article
- Ligand binding and allostery can emerge simultaneously.Protein science : a publication of the Protein Society · 2007Article
- Guanidinium derivatives bind preferentially and trigger long-distance conformational changes in an engineered T4 lysozyme.Protein science : a publication of the Protein Society · 2006Article
- Protein stabilization by specific binding of guanidinium to a functional arginine-binding surface on an SH3 domain.Protein science : a publication of the Protein Society · 2006Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have designed a molecular switch in a T4 lysozyme construct that controls a large-scale translation of a duplicated helix. As shown by crystal structures of the construct with the switch on and off, the conformational change is triggered by the binding of a ligand (guanidinium ion) to a site that in the wild-type protein was occupied by the guanidino head group of an Arg. In the design template, a duplicated helix is flanked by two loop regions of different stabilities. In the "on" state, the N-terminal loop is weakly structured, whereas the C-terminal loop has a well defined conformation that is stabilized by means of nonbonded interactions with the Arg head group. The truncation of the Arg to Ala destabilizes this loop and switches the protein to the "off" state, in which the duplicated helix is translocated approximately 20 A. Guanidinium binding restores the key interactions, restabilizes the C-terminal loop, and restores the "on" state. Thus, the presence of an external ligand, which is unrelated to the catalytic activity of the enzyme, triggers the inserted helix to translate 20 A away from the binding site. The results illustrate a proposed mechanism for protein evolution in which sequence duplication followed by point mutation can lead to the establishment of new function.
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