In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 10 ( 2001-05-08), p. 5590-5595
Abstract:
The structural changes accompanying stretch-induced early unfolding
events were investigated for the four type III fibronectin (FN-III) modules, FN-III 7 , FN-III 8 , FN-III 9 ,
and FN-III 10 by using steered molecular dynamics.
Simulations revealed that two main energy barriers, I and II, have to be overcome to initiate unraveling of FN-III's tertiary structure. In
crossing the first barrier, the two opposing β-sheets of FN-III are rotated against each other such that the β-strands of both β-sheets
align parallel to the force vector (aligned state). All further events in the unfolding pathway proceed from this intermediate state. A second
energy barrier has to be overcome to break the first major cluster of hydrogen bonds between adjacent β-strands. Simulations revealed that
the height of barrier I varied significantly among the four modules studied, being largest for FN-III 7 and lowest for
FN-III 10 , whereas the height of barrier II showed little
variation. Key residues affecting the mechanical stability of FN-III modules were identified. These results suggest that FN-III modules can
be prestretched into an intermediate state with only minor changes to their tertiary structures. FN-III 10 , for example, extends
12 Å from the native “twisted” to the intermediate aligned state, and an additional 10 Å from the aligned state to further
unfolding where the first β-strand is peeled away. The implications of the existence of intermediate states regarding the elasticity of
fibrillar fibers and the stretch-induced exposure of cryptic sites are discussed.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.101582198
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2001
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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