Apr 18 15:00 Understanding the Unusual Biological Function and Action Mechanism of the acid resistant molecular chaperone HdeA: from in vitro to in vivo
Speaker:Zengyi Chang
Host:Prof. Mingyao Liu
When:2014-4-18 15:00
Where:Conference Room 534, School of Life Sciences
Abstract:The hdeA gene of E. coli was found to be acid inducible and was revealed by genetic studies to be important for the acid survival of the strain. We revealed that HdeA employs a novel strategy to modulate its chaperone activity: it possesses an ordered conformation that is unable to bind denatured substrate proteins at neutral pH, but transforms into a globally disordered conformation that is able to bind substrate proteins at a pH below 3. The conserved ‘amphiphilic’ feature of HdeA, i.e. the exposure of the conserved hydrophobic region and highly charged terminal regions, is essential for exhibiting chaperone-like activity under extremely low pH conditions. Using a highly efficient protein photocrosslinking probe, we characterized the proteins interacting with HdeA in living E. coli cells exposed to low pH conditions and revealed a unique chaperone-protecting-chaperone mechanism, in which HdeA protects DegP and SurA initially, allowing the latter to assist the HdeA-mediated acid recovery.
References:
1. Hong, W., et al., (2005) Periplasmic protein HdeA exhibits chaperone-like activity exclusively within stomach pH range by transforming into disordered conformation, J. Biol Chem., 280:27029-27034.
2. Wu, Y., et al., (2008) Conserved amphiphilic feature Is essential for periplasmic chaperone HdeA to support Acid resistance in enteric bacteria, Biochem. J., 412:389-397.
3. Zhang, M. et al., (2011) A genetically incorporated crosslinker reveals chaperone cooperation in acid resistance, Nat. Chem. Biol., 7:671-677. (Cover article)
4. Hong, W. et al. (2012), Chaperone-dependent mechanisms for acid resistance in enteric bacteria, Trends in Microbiology, 20:328-335 (invited review)