A delicate interplay of structure, dynamics, and thermodynamics for function: a high pressure NMR study of outer surface protein A.

ABSTRACT: Outer surface protein A (OspA) is a crucial protein in the infection of Borrelia burgdorferi causing Lyme disease. We studied conformational fluctuations of OspA with high-pressure (15)N/(1)H two-dimensional NMR along with high-pressure fluorescence spectroscopy. We found evidence within folded, native OspA for rapid local fluctuations of the polypeptide backbone in the nonglobular single layer ?-sheet connecting the N- and C-terminal domains with ? << ms, which may give the two domains certain independence in mobility and thermodynamic stability. Furthermore, we found that folded, native OspA is in equilibrium (? >> ms) with a minor conformer I, which is almost fully disordered and hydrated for the entire C-terminal part of the polypeptide chain from ?8 to the C-terminus. Conformer I is characterized with ?G(0) = 32 ± 9 kJ/mol and ?V(0) = -140 ± 40 mL/mol, populating only ?0.001% at 40°C at 0.1 MPa, pH 5.9. Because in the folded conformer the receptor binding epitope of OspA is buried in the C-terminal domain, its transition into conformer I under in vivo conditions may be critical for the infection of B. burgdorferi. The formation and stability of the peculiar conformer I are apparently supported by a large packing defect or cavity located in the C-terminal domain.

SUBMITTER: Kitahara R 

PROVIDER: S-EPMC3283806 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature