title: Direct observations of shifts in the β-sheet register of a protein-peptide complex using explicit solvent simulations.
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.
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Panteva
authors.forename: Reza
authors.initials: R
authors.lastname: Salari
authors.forename: Monica
authors.initials: M
authors.lastname: Bhattacharjee
authors.forename: Lillian T
authors.initials: LT
authors.lastname: Chong
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry*; D019394:Ki-67 Antigen / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012997:Solvents / Q000737:chemistry*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; C492406:NIFK protein, human; D009687:Nuclear Proteins; D012997:Solvents