title: Aromatic claw: A new fold with high aromatic content that evades structural prediction.
abstract: 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.
authors.affiliation: Biomolecular NMR Core Facility, University of Chicago, Chicago, Illinois.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Sachleben
authors.affiliation: Department of Chemistry, University of Chicago, Chicago, Illinois.
authors.forename: Aashish N
authors.initials: AN
authors.lastname: Adhikari
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Gawlak
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hoey
authors.affiliation: 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.
authors.forename: Gaohua
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois.|Biological Sciences Division, Argonne National Laboratory, Argonne, Illinois.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Joachimiak
authors.affiliation: 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.
authors.forename: Gaetano T
authors.initials: GT
authors.lastname: Montelione
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois.
authors.forename: Tobin R
authors.initials: TR
authors.lastname: Sosnick
authors.affiliation: 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.
authors.forename: Shohei
authors.initials: S
authors.lastname: Koide
mesh_terms: D001419:Bacteria / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D017510:Protein Folding; D017433:Protein Structure, Secondary; D014364:Tryptophan / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D014364:Tryptophan
keywords: Aq1974; Aquifex aeolicus; CASP; NMR; aromatic claw; protein folding; protein structure