Aromatic claw: A new fold with high aromatic content that evades structural prediction: Aromatic Claw
- Biomolecular NMR Core Facility, University of Chicago, Chicago Illinois
- Department of Chemistry, University of Chicago, Chicago Illinois
- Department of Biochemistry and Molecular Biology, University of Chicago, Chicago Illinois
- Northeast Structural Genomics Consortium (NESG), Department of Molecular Biology and Biochemistry, School of Arts and Sciences, and Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, and Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway New Jersey
- Department of Biochemistry and Molecular Biology, University of Chicago, Chicago Illinois; Biological Sciences Division, Argonne National Laboratory, Argonne Illinois
- Department of Biochemistry and Molecular Biology, University of Chicago, Chicago Illinois; Department of Biochemistry and Molecular Pharmacology and the Perlmutter Cancer Center, New York University School of Medicine, New York New York
We determined the NMR structure of a highly aromatic (13%) protein of unknown function, Aq1974 from Aquifex aeolicus (PDB ID: 5SYQ). The unusual sequence of this protein has a tryptophan content five times the normal (six tryptophan residues of 114 or 5.2% while the average tryptophan content is 1.0%) with the tryptophans occurring in a WXW motif. It has no detectable sequence homology with known protein structures. Although its NMR spectrum suggested that the protein was rich in β-sheet, upon resonance assignment and solution structure determination, the protein was found to be primarily α-helical with a small two-stranded β-sheet with a novel fold that we have termed an Aromatic Claw. As this fold was previously unknown and the sequence unique, we submitted the sequence to CASP10 as a target for blind structural prediction. At the end of the competition, the sequence was classified a hard template based model; the structural relationship between the template and the experimental structure was small and the predictions all failed to predict the structure. CSRosetta was found to predict the secondary structure and its packing; however, it was found that there was little correlation between CSRosetta score and the RMSD between the CSRosetta structure and the NMR determined one. This work demonstrates that even in relatively small proteins, we do not yet have the capacity to accurately predict the fold for all primary sequences. The experimental discovery of new folds helps guide the improvement of structural prediction methods.
- Research Organization:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Organization:
- National Institutes of Health (NIH)
- DOE Contract Number:
- AC02-06CH11357
- OSTI ID:
- 1393926
- Journal Information:
- Protein Science, Vol. 26, Issue 2; ISSN 0961-8368
- Publisher:
- The Protein Society
- Country of Publication:
- United States
- Language:
- English
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