Premium
Probing the Beta‐Amyloid Structure and Function of Hemolysin A
Author(s) -
Wawrzyn Grayson Thomas,
Werren Rebecca
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.650.2
Subject(s) - chemistry , hemolysis , beta (programming language) , hemolysin , monomer , crystallography , biophysics , disulfide bond , protein structure , stereochemistry , biochemistry , biology , polymer , organic chemistry , virulence , computer science , gene , immunology , programming language
In this study we aimed to analyze the structure and function of a truncated form of hemolysin A from Proteus mirabilis using a combination of template‐assisted hemolysis and x‐ray crystallography. The hemolysis assay performed in the presence of both truncated and full‐length hemolysin A noted a cross‐seeded, biphasic activity profile, where the biphasic nature could be eliminated upon pre‐incubation of the protein components in the absence of red blood cells. X‐ray structure analysis of truncated hemolysin A reported a right‐handed parallel beta‐helix fold with three adjoining segments of anti‐parallel beta‐sheet, three buried solvent molecules near the disulfide bond between cysteines 144 and 147, and a unique dry dimeric interface. The disulfide bond stabilizes a unique beta‐arc between beta‐strands 11 and 12, which form two sides of the third full solenoid turn within right‐handed beta‐helix. The unusual dry dimeric interface propagates the monomeric beta‐helix structure forming a fibril appearance. The biochemical and structural results are discussed in reference to the propagation of beta‐amyloid type infectious prion diseases via a template‐assisted model.