Interpenetrating Cubes in the X-ray Crystallographic Structure of a Peptide Derived from Medin19-36

J Am Chem Soc. 2020 Sep 16;142(37):15870-15875. doi: 10.1021/jacs.0c06143. Epub 2020 Sep 3.

Abstract

Amyloidogenic peptides and proteins are rich sources of supramolecular assemblies. Sequences derived from well-known amyloids, including Aβ, human islet amyloid polypeptide, and tau have been found to assemble as fibrils, nanosheets, ribbons, and nanotubes. The supramolecular assembly of medin, a 50-amino acid peptide that forms fibrillary deposits in aging human vasculature, has not been heavily investigated. In this work, we present an X-ray crystallographic structure of a cyclic β-sheet peptide derived from the 19-36 region of medin that assembles to form interpenetrating cubes. The edge of each cube is composed of a single peptide, and each vertex is occupied by a divalent metal ion. This structure may be considered a metal-organic framework (MOF) containing a large peptide ligand. This work demonstrates that peptides containing Glu or Asp that are preorganized to adopt β-hairpin structures can serve as ligands and assemble with metal ions to form MOFs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Amyloid beta-Peptides / chemistry*
  • Crystallography, X-Ray
  • Humans
  • Models, Molecular
  • Protein Conformation

Substances

  • Amyloid beta-Peptides