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| 2. |
- Akke, Mikael, et al.
(författare)
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An open and shut case
- 2001
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Ingår i: Nature Structural Biology. - : Springer Science and Business Media LLC. - 1072-8368. ; 8:11, s. 910-912
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Tidskriftsartikel (refereegranskat)abstract
- A powerful new NMR technique applied to the ubiquitous Ca2+ sensor, calmodulin, reveals significant conformational flexibility within each globular domain, which contributes to its ability to bind a wide range of targets. These measurements of residual dipolar couplings between nuclear spins demonstrate a fast and accurate method for pinpointing structural features that cannot be delineated reliably by traditional NOE analysis.
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| 6. |
- Janowski, Robert, et al.
(författare)
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Human cystatin C, an amyloidogenic protein, dimerizes through three-dimensional domain swapping
- 2001
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Ingår i: Nature Structural Biology. - : Springer Science and Business Media LLC. - 1072-8368. ; 8:4, s. 316-320
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Tidskriftsartikel (refereegranskat)abstract
- The crystal structure of human cystatin C, a protein with amyloidogenic properties and a potent inhibitor of cysteine proteases, reveals how the protein refolds to produce very tight two-fold symmetric dimers while retaining the secondary structure of the monomeric form. The dimerization occurs through three-dimensional domain swapping, a mechanism for forming oligomeric proteins. The reconstituted monomer-like domains are similar to chicken cystatin except for one inhibitory loop that unfolds to form the open interface of the dimer. The structure explains the tendency of human cystatin C to dimerize and suggests a mechanism for its aggregation in the brain arteries of elderly people with amyloid angiopathy. A more severe conformational disease is associated with the L68Q mutant of human cystatin C, which causes massive amyloidosis, cerebral hemorrhage and death in young adults. The structure of the three-dimensional domain-swapped dimers shows how the L68Q mutation destabilizes the monomers and makes the partially unfolded intermediate less unstable. Higher aggregates may arise through the three-dimensional domain-swapping mechanism occurring in an open-ended fashion in which partially unfolded molecules are linked into infinite chains.
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| 10. |
- Lindberg, Magnus, et al.
(författare)
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Complete change of the protein folding transition state upon circular permutation
- 2002
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Ingår i: Nature Structural Biology. - : Springer Science and Business Media LLC. - 1072-8368. ; 9, s. 818-22
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Tidskriftsartikel (refereegranskat)abstract
- Reversing the loop lengths of the small protein S6 by circular permutation has a dramatic effect on the transition state structure: it changes from globally diffuse to locally condensed. The phenomenon arises from a biased dispersion of the contact energies. Stability data derived from point mutations throughout the S6 structure show that interactions between residues that are far apart in sequence are stronger than those that are close. This entropy compensation drives all parts of the protein to fold simultaneously and produces the diffuse transition-state structure typical for two-state proteins. In the circular permutant, where strong contacts and short sequence separations are engineered to concur, the transition state becomes atypically condensed and polarized. Taken together with earlier findings that S6 may also fold by a 'collapsed' trajectory with an intermediate, the results suggest that this protein may fold by a multiplicity of mechanisms. The observations indicate that the diffuse transition state of S6 is not required for folding but could be an evolutionary development to optimize cooperativity.
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