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 PUF2 are unfolding excursions that start from native apoflavodoxin but do not continue to the unfolded state. PUF3 and PUF4 could be similar excursions, but their rates of formation suggest that they are on a dead-end folding route that starts from unfolded apoflavodoxin and does not continue all of the way to native protein. All PUFs detected thus are off the protein's productive folding route.

authors

Bollen YJ,Kamphuis MB,van Mierlo CP

doi

10.1073/pnas.0509133103

keywords:

subject

Has Abstract

pub_date

2006-03-14 00:00:00

pages

4095-100

issue

11

eissn

0027-8424

issn

1091-6490

pii

0509133103

journal_volume

103

pub_type

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