Helicobacter pylori cell binding factor 2: Insights into domain motion

Area of Science:

• Microbiology
• Structural Biology
• Biochemistry

Background:

• Helicobacter pylori cell binding factor 2 (HpCBF2) is an antigenic virulence factor.
• HpCBF2 belongs to the SurA-like peptidyl-prolyl cis-trans isomerase family, impacting gastrointestinal tract pathogenicity.
• HpCBF2 exhibits peptidyl-prolyl cis-trans isomerase (PPIase) activity and may function as a periplasmic chaperone.

Purpose of the Study:

• To measure the isomerization and chaperone activity of HpCBF2.
• To determine the crystal structure of HpCBF2 in complex with an inhibitor.
• To investigate the structural basis for HpCBF2's function.

Main Methods:

• X-ray crystallography at 2.4Å resolution to determine the structure of HpCBF2-inhibitor complex.
• Measurement of HpCBF2's isomerization and chaperone activity.
• Small-angle X-ray scattering (SAXS) experiments to analyze domain motion.

Main Results:

• The crystal structure revealed HpCBF2 as a homodimer with a central hydrophobic cavity.
• Each monomer comprises a PPIase and a chaperone domain, with chaperone domains exhibiting a domain-swap.
• SAXS data indicated domain motion between apo- and inhibitor-bound states, suggesting flexibility for peptide binding.

Conclusions:

• HpCBF2 forms a unique homodimeric structure with distinct PPIase and chaperone domains.
• The observed domain motion is likely essential for both PPIase activity and chaperone-mediated refolding.
• Understanding HpCBF2 structure and dynamics offers insights into H. pylori pathogenicity and potential therapeutic targets.