Author
Listed:
- Menahem Pirchi
(Weizmann Institute of Science)
- Guy Ziv
(Weizmann Institute of Science
Present address: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey 08544, USA.)
- Inbal Riven
(Weizmann Institute of Science)
- Sharona Sedghani Cohen
(Weizmann Institute of Science)
- Nir Zohar
(Weizmann Institute of Science)
- Yoav Barak
(Chemical Research Support, Weizmann Institute of Science)
- Gilad Haran
(Weizmann Institute of Science)
Abstract
Proteins attain their function only after folding into a highly organized three-dimensional structure. Much remains to be learned about the mechanisms of folding of large multidomain proteins, which may populate metastable intermediate states on their energy landscapes. Here we introduce a novel method, based on high-throughput single-molecule fluorescence experiments, which is specifically geared towards tracing the dynamics of folding in the presence of a plethora of intermediates. We employ this method to characterize the folding reaction of a three-domain protein, adenylate kinase. Using thousands of single-molecule trajectories and hidden Markov modelling, we identify six metastable states on adenylate kinase's folding landscape. Remarkably, the connectivity of the intermediates depends on denaturant concentration; at low concentration, multiple intersecting folding pathways co-exist. We anticipate that the methodology introduced here will find broad applicability in the study of folding of large proteins, and will provide a more realistic scenario of their conformational dynamics.
Suggested Citation
Menahem Pirchi & Guy Ziv & Inbal Riven & Sharona Sedghani Cohen & Nir Zohar & Yoav Barak & Gilad Haran, 2011.
"Single-molecule fluorescence spectroscopy maps the folding landscape of a large protein,"
Nature Communications, Nature, vol. 2(1), pages 1-7, September.
Handle:
RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1504
DOI: 10.1038/ncomms1504
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