Protein tandem repeats: the more perfect the less structured

By Julien Jorda, Bin Xue, Vladimir N Uversky, A. Kajava. 2010

131 citations recorded by the source corpus.

We analysed the structural properties of protein regions containing arrays of perfect and nearly perfect tandem repeats. Naturally occurring proteins with perfect repeats are practically absent among the proteins with known 3D structures. The great majority of such regions in the Protein Data Bank are found in the proteins designed de novo. The abundance of natural structured proteins with tandem repeats is inversely correlated with the repeat perfection: the chance of finding natural structured proteins in the Protein Data Bank increases with a decrease in the level of repeat perfection. Prediction of intrinsic disorder within the tandem repeats in the SwissProt proteins supports the conclusion that the level of repeat perfection correlates with their tendency to be unstructured. This correlation is valid across the various species and subcellular localizations, although the level of disordered tandem repeats varies significantly between these datasets. On average, in prokaryotes, tandem repeats of cytoplasmic proteins were predicted to be the most structured, whereas in eukaryotes, the most structured portion of the repeats was found in the membrane proteins. Our study supports the hypothesis that, in general, the repeat perfection is a sign of recent evolutionary events rather than of exceptional structural and (or) functional importance of the repeat residues.

Subfields: Molecular Biology

Citations in the corpus

• The Pfam protein families database in 2019 (2018, neutral): “Nevertheless, perfect repeats in engineered sequences do exist and ironically, often correlate with a tendency to be unstructured (18).”
• Computational design of a self-assembling symmetrical β-propeller protein (2014, unknown): “In fact, a search for identical sequence repeats within the same polypeptide chain failed to find any duplicated domains containing regular secondary structure in known natural proteins (26).”
• Intrinsically Disordered Proteins and Their “Mysterious” (Meta)Physics (2019, unknown): “in order-promoting residues (Trp, Cys, Tyr, Ile, Phe, Val, Asn, and Leu) and enriched in disorder-promoting residues (Arg, Pro, Gln, Gly, Glu, Ser, Ala, and Lys) (see Figure 2A) [4, 49, 51–56] and commonly contain repeats [57, 58].”
• RepeatsDB 2.0: improved annotation, classification, search and visualization of repeat protein structures (2016, unknown): “The process of duplication originating new repeats is error-prone and identical flanking repeat units have an intrinsic tendency to diverge (13).”
• DECIPHER: harnessing local sequence context to improve protein multiple sequence alignment (2015, unknown): “These changes in score were unexpected, as structural benchmarks do not consider most gapped regions since they often occur in parts of the structure that are difficult to superimpose [17], and repeats tend to be found in disordered protein regions [64].”
• How Common Is Disorder? Occurrence of Disordered Residues in Four Domains of Life (2015, unknown): “Most of such patterns comprise amino acid motifs with low complexity, including homo-repeats that are known to be disordered [8,9].”