REPPER--repeats and their periodicities in fibrous proteins

Abstract

REPPER (REPeats and their PERiodicities) is an integrated server that detects and analyzes regions with short gapless repeats in protein sequences or alignments. It finds periodicities by Fourier Transform (FTwin) and internal similarity analysis (REPwin). FTwin assigns numerical values to amino acids that reflect certain properties, for instance hydrophobicity, and gives information on corresponding periodicities. REPwin uses self-alignments and displays repeats that reveal significant internal similarities. Both programs use a sliding window to ensure that different periodic regions within the same protein are detected independently. FTwin and REPwin are complemented by secondary structure prediction (PSIPRED) and coiled coil prediction (COILS), making the server a versatile analysis tool for sequences of fibrous proteins. REPPER is available at http://protevo.eb.tuebingen.mpg.de/repper.

Figure 1

REPPER analysis of YadA. (a) FTwin output showing periodicities along the sequence; level of significance color-coded from yellow to blue. When clicking on a colored bar, a Fourier spectrum is calculated for this part of the sequence (see spectra for the head and stalk domain). (b) REPwin output displaying periodicities along the sequence. The head domain with periodicity 14 and the stalk domain with periodicity 15 are clearly distinguished. (c) PSIPRED output; α-helices are displayed in red, β-sheets in green. (d) COILS output with intermediate probabilities for the stalk domain (window sizes: red, 28; blue, 21; green, 14).

Figure 2

FTwin periodicities in multiple-sequence mode differ from those in single-sequence mode (window size 50, threshold parameter 3). (a) FTwin output for the cortexillin single sequence (PDB: 1D7M). The characteristic periodicity of 7/2 = 3.5 is not detected. (b) FTwin output for a cortexillin multiple sequence alignment (based on Blast hits with E-value cutoff 10⁻⁴ over the NCBI nonredundant protein database). It reveals the dominant periodicity of 3.5 over a substantial part of the protein and a periodicity of 7/3 = 2.3. The exact periodicities are shown when clicking on the colored bars.

Figure 3

Comparison between COILS in single-sequence mode and in multiple-sequence mode (window sizes: red, 28; blue, 21; green, 14). (a) Structure of the Bag domain (PDB: 1HX1) showing the three coiled-coil-like helices H1–H3 (21). (b) COILS output for the Bag domain single sequence. (c) COILS output for a multiple sequence alignment (based on Blast hits of the Bag domain sequence with E-value cutoff 10⁻⁴ over the NCBI nonredundant protein database filtered to 70% sequence identity with no low-complexity regions).