Abstract
Determining the three-dimensional structures of macromolecules is a major goal of biological research, because of the close relationship between structure and function; however, thousands of protein domains still have unknown structures. Structure determination usually relies on physical techniques including X-ray crystallography, NMR spectroscopy and cryo-electron microscopy. Here we present a method that allows the high-resolution three-dimensional backbone structure of a biological macromolecule to be determined only from measurements of the activity of mutant variants of the molecule. This genetic approach to structure determination relies on the quantification of genetic interactions (epistasis) between mutations and the discrimination of direct from indirect interactions. This provides an alternative experimental strategy for structure determination, with the potential to reveal functional and in vivo structures.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / chemistry*
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism
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Bacterial Proteins / chemistry*
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism
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Epistasis, Genetic*
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Humans
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Mutagenesis*
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Mutation*
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Poly(A)-Binding Proteins / chemistry*
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Poly(A)-Binding Proteins / genetics
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Poly(A)-Binding Proteins / metabolism
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Protein Conformation
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Protein Domains
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Protein Interaction Domains and Motifs
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RNA, Catalytic / chemistry*
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RNA, Catalytic / genetics
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RNA, Catalytic / metabolism
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Saccharomyces cerevisiae Proteins / chemistry*
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Transcription Factors / chemistry*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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YAP-Signaling Proteins
Substances
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Adaptor Proteins, Signal Transducing
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Bacterial Proteins
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IgG Fc-binding protein, Streptococcus
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Poly(A)-Binding Proteins
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RNA, Catalytic
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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YAP-Signaling Proteins
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YAP1 protein, human
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pab1 protein, S cerevisiae