Direct observations of shifts in the β-sheet register of a protein-peptide complex using explicit solvent simulations

Biophys J. 2011 May 4;100(9):L50-2. doi: 10.1016/j.bpj.2011.03.035.

Abstract

Using explicit solvent molecular dynamics simulations, we were able to obtain direct observations of shifts in the hydrogen-bonding register of an intermolecular β-sheet protein-peptide complex. The β-sheet is formed between the FHA domain of cancer marker protein Ki67 (Ki67FHA) and a peptide fragment of the hNIFK signaling protein. Potential encounter complexes of the Ki67FHA receptor and hNIFK peptide are misregistered states of the β-sheet. Rearrangements of one of these misregistered states to the native state were captured in three independent simulations. All three rearrangements occurred by a common mechanism: an aromatic residue of the peptide (F263) anchors into a transient hydrophobic pocket of the receptor to facilitate the formation of native hydrogen bonds. To our knowledge, these simulations provide the first atomically detailed visualizations of a mechanism by which nature might correct for errors in the alignment of intermolecular β-sheets.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Computer Simulation*
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry*
  • Ki-67 Antigen / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Solvents / chemistry*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Ki-67 Antigen
  • NIFK protein, human
  • Nuclear Proteins
  • Solvents