The structural basis of mode of activation and functional diversity: A case study with HtrA family of serine proteases

HtrA (High temperature requirement protease A) proteins that are primarily involved in protein quality control belong to a family of serine proteases conserved from bacteria to humans. HtrAs are oligomeric proteins that share a common trimeric pyramidal architecture where each monomer comprises a serine protease domain and one or two PDZ domains. Although the overall structural integrity is well maintained and they exhibit similar mechanism of activation, subtle conformational changes and structural plasticity especially in the flexible loop regions and domain interfaces lead to differences in their active site conformation and hence in their specificity and functions.

► HtrAs are protein quality control proteases conserved from prokaryotes to humans.
► HtrA proteins are stable trimers but usually form higher order oligomers.
► Subtle structural changes and PDZ domain plasticity lead to functional diversity.
► Perform variety of biological functions and are implicated in several diseases.