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Aromatic claw: A new fold with high aromatic content that evades structural prediction
Author(s) -
Sachleben Joseph R.,
Adhikari Aashish N.,
Gawlak Grzegorz,
Hoey Robert J.,
Liu Gaohua,
Joachimiak Andrzej,
Montelione Gaetano T.,
Sosnick Tobin R.,
Koide Shohei
Publication year - 2017
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.3069
Subject(s) - protein secondary structure , protein data bank (rcsb pdb) , tryptophan , homology modeling , protein structure prediction , protein structure , crystallography , structural genomics , chemistry , structural motif , protein primary structure , sequence (biology) , biology , computational biology , peptide sequence , biochemistry , amino acid , enzyme , gene
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.