Author | Ahn, Hee-Chul | en_US |
Author | Le, Yen T. H. | en_US |
Author | Nagchowdhuri, Partha S. | en_US |
Author | Derose, Eugene F. | en_US |
Author | Putnam-Evans, Cindy | en_US |
Author | London, Robert E. | en_US |
Author | Markley, John L. | en_US |
Author | Lim, Kwang Hun | en_US |
Date Accessioned | 2011-02-04T19:48:44Z | en_US |
Date Accessioned | 2011-05-17T14:43:50Z | |
Date Available | 2011-02-04T19:48:44Z | en_US |
Date Available | 2011-05-17T14:43:50Z | |
Date of Issue | 2006-11 | en_US |
Identifier (Citation) | Protein Science; 15:11 p. 2552-2557 | en_US |
Identifier (URI) | http://hdl.handle.net/10342/3198 | en_US |
Description | Amyloid formation is associated with structural changes of native polypeptides to monomeric intermediate states and their self-assembly into insoluble aggregates. Characterizations of the amyloidogenic
intermediate state are, therefore, of great importance in understanding the early stage of amyloidogenesis. Here, we present NMR investigations of the structural and dynamic properties of the acid-unfolded amyloidogenic intermediate state of the phosphatidylinositol 3-kinase (PI3K) SH3 domain—a model peptide. The monomeric amyloidogenic state of the SH3 domain studied at pH 2.0 (35°C) was shown to be substantially disordered with no secondary structural preferences. 15N NMR relaxation experiments indicated that the unfolded polypeptide is highly flexible on a subnanosecond
timescale when observed under the amyloidogenic condition (pH 2.0, 35°C). However, more restricted motions were detected in residues located primarily in the b-strands as well as in a loop in the native
fold. In addition, nonnative long-range interactions were observed between the residues with the reduced flexibility by paramagnetic relaxation enhancement (PRE) experiments. These indicate that the
acid-unfolded state of the SH3 domain adopts a partly folded conformation through nonnative longrange contacts between the dynamically restricted residues at the amyloid-forming condition. Originally published Protein Science, Vol. 15, No. 11, Nov 2006 | en_US |
Language | en_US | en_US |
Publisher | East Carolina University | en_US |
Related URI | http://onlinelibrary.wiley.com/doi/10.1110/ps.062154306/abstract;jsessionid=0F7196949CCE21C6D61089C8168C3A46.d03t04 | en_US |
Rights | Author notified of opt-out rights by Cammie Jennings | en_US |
Subject | Amyloids | en_US |
Subject | PI3K SH3 | en_US |
Subject | NMR | en_US |
Subject | Dynamics | en_US |
Subject | Amyloidogenic intermediate | en_US |
Subject | Long-range interactions | en_US |
Subject | PRE | en_US |
Title | NMR characterizations of an amyloidogenic conformational ensemble of the PI3K SH3 domain | en_US |
Type | Article | en_US |
Identifier (PMID) | PMC2242406 | en_US |
Identifier (DOI) | 10.1110/ps.062154306 | |