On the border of the amyloidogenic sequences: prefix analysis of the parallel beta sheets in the PDB_Amyloid collection

Abstract

The Protein Data Bank (PDB) today contains more than 174,000 entries with the 3-dimensional structures of biological macromolecules. Using the rich resources of this repository, it is possible identifying subsets with specific, interesting properties for different applications. Our research group prepared an automatically updated list of amyloid- and probably amyloidogenic molecules, the PDB_Amyloid collection, which is freely available at the address http://pitgroup.org/amyloid. This resource applies exclusively the geometric properties of the steric structures for identifying amyloids. In the present contribution, we analyze the starting (i.e., prefix) subsequences of the characteristic, parallel beta-sheets of the structures in the PDB_Amyloid collection, and identify further appearances of these length-5 prefix subsequences in the whole PDB data set. We have identified this way numerous proteins, whose normal or irregular functions involve amyloid formation, structural misfolding, or anti-coagulant properties, simply by containing these prefixes: including the T-cell receptor (TCR), bound with the major histocompatibility complexes MHC-1 and MHC-2; the p53 tumor suppressor protein; a mycobacterial RNA polymerase transcription initialization complex; the human bridging integrator protein BIN-1; and the tick anti-coagulant peptide TAP.

Keywords: PDB; amyloid; amyloid-precursor; amyloidogenic proteins; prefix; suffix.

Figure 1:

PDB entry 2MPZ, depicted with PyMol. Yellow color denotes β-sheets. The QKLVF prefix, where QK is green (it is not a part of the parallel β-sheet) and LVF is yellow (i.e., LVF are the first three residues of the parallel β-segment), is emphasized at the right bottom of the figure, while its corresponding sequence at the top center.

Figure 2:

PDB entry 1OLG, depicted with PyMol. Yellow color denotes β-sheets. The GEYFT prefix, where GE are green (it is not a part of the parallel β-sheet) and YFT are yellow (i.e., YFT are the first three residues of the parallel β-segment), is emphasized at the left middle section of the figure, while its corresponding sequence at the lower left corner.

Figure 3:

PDB entry 2FIC: the BAR domain of the human Bin1/amphiphysin II, depicted with PyMol. The red colored sections of the α-helices correspond to the HQKLV subsequence.

Figure 4:

PDB entry 1TCP: the tick anticoagulant peptide (TAP), depicted with PyMol. The blue-colored section correspond to the GGERA prefix: GG preceeding the first three residues, ERA, in the β-sheet.