title: A mechanism of action for small heat shock proteins.
abstract: Molecular dynamics simulations of a fitted multimeric structure of Mycobacterium tuberculosis α-crystallin (Mtb Acr) identify solvent exclusion from the β(4)-β(8) hydrophobic groove as a critical factor driving subunit assembly. Dehydration is also implicated as a determinant factor governing the chaperone activity of the dimer upon its dissociation from the oligomer. Two exposed hydrogen bonds, responsible for stabilizing the β(8)-β(9) fold are identified as key mechanistic elements in this process. Based on the overproduction of the chemokine CXCL16, observed after macrophage exposure to Mtb Acr, the proteases ADAM10 and ADAM17 are mooted as possible targets of this chaperone activity.
authors.affiliation: Department of Chemistry, St. Edward's University, Austin, TX 78704, USA. healy@stedwards.edu
authors.forename: Eamonn F
authors.initials: EF
authors.lastname: Healy
authors.forename: Peter J
authors.initials: PJ
authors.lastname: King
mesh_terms: D051722:ADAM Proteins / Q000737:chemistry; D000072197:ADAM10 Protein; D000072198:ADAM17 Protein; D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases / Q000737:chemistry; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D050888:Heat-Shock Proteins, Small / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D008565:Membrane Proteins / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis; D017433:Protein Structure, Secondary; D051116:Receptors, Scavenger; D038201:alpha-Crystallins / Q000737:chemistry*
chemical_list: C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D050888:Heat-Shock Proteins, Small; D008565:Membrane Proteins; D051116:Receptors, Scavenger; D038201:alpha-Crystallins; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human