An evolutionary strategy for highly efficient secretion of multidomain Staphylococcal protein A: N- to C-terminal stability gradient

A steep N- to C-terminal stability gradient across Staphylococcal protein A domains (0.97 ± 0.05 to 5.69 ± 0.28 kcal/mol) is linked to efficient co-translational secretion through SecYEG.

• Why it matters: SpA is a key virulence factor and therapeutic target, but how its multidomain stability supports secretion is unclear, especially beyond characterized domains B and E.
• What they did: Using intrinsic fluorescence with urea denaturation, the folding thermodynamics of isolated domains and the native N-terminal half (SpA-N) were measured, and B-domain repeat constructs were analyzed with a nearest-neighbor matrix model.
• The result: Domains D, A, B, and C show identical stabilities in isolation and in SpA-N, E is stabilized by ~1 kcal/mol in context, adjacent domains are thermodynamically uncoupled, and the gradient is proposed to facilitate SecYEG translocation.