The folding energy landscape of apoflavodoxin is rugged: hydrogen exchange reveals nonproductive misfolded intermediates.

ABSTRACT: Many native proteins occasionally form partially unfolded forms (PUFs), which can be detected by hydrogen/deuterium exchange and NMR spectroscopy. Knowledge about these metastable states is required to better understand the onset of folding-related diseases. So far, not much is known about where PUFs reside within the energy landscape for protein folding. Here, four PUFs of the relatively large apoflavodoxin (179 aa) are identified. Remarkably, at least three of them are partially misfolded conformations. The misfolding involves side-chain contacts as well as the protein backbone. The rates at which the PUFs interconvert with native protein have been determined. Comparison of these rates with stopped-flow data positions the PUFs in apoflavodoxin's complex folding energy landscape. PUF1 and

SUBMITTER: Bollen YJ 

PROVIDER: S-EPMC1449652 | biostudies-literature | 2006 Mar

REPOSITORIES: biostudies-literature