Disorder in cholesterol-binding functionality of CRAC peptides: a molecular dynamics study. Academic Article uri icon


  • The cholesterol recognition/interaction amino acid consensus (CRAC) motif is a primary structure pattern used to identify regions that may be responsible for preferential cholesterol binding in many proteins. The leukotoxin LtxA, which is produced by a pathogenic bacterium, contains two CRAC seqences, only one of which is responsible for cholesterol binding, and the binding is required for cytotoxicity. The factors, in addition to the CRAC definition, that may be responsible for cholesterol-binding functionality and atomistic interactions between the CRAC region and cholesterol are as yet unknown. This study uses molecular dynamics simulations to identify structural characteristics and specific interactions of the two LtxA CRAC peptides with both pure phospholipid and binary cholesterol-phospholipid bilayers. We have identified changes in the secondary structure of these peptides that occur upon cholesterol binding, which are not seen when it is associated with a cholesterol-devoid membrane, and which show salient coupling of structural disorder and function. Additionally, the central tyrosine residue of the CRAC motif was found to play a significant role in cholesterol binding, though residues outside of the CRAC motif also influence membrane interactions and functionality of the CRAC region.

published proceedings

  • J Phys Chem B

altmetric score

  • 0.5

author list (cited authors)

  • Miller, C. M., Brown, A. C., & Mittal, J.

citation count

  • 27

complete list of authors

  • Miller, Cayla M||Brown, Angela C||Mittal, Jeetain

publication date

  • November 2014