NMR characterizations of an amyloidogenic conformational ensemble of the PI3K SH3 domain.

NMR characterizations of an amyloidogenic conformational ensemble of the PI3K SH3 domain. Research Abstract Details 

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NMR characterizations of an amyloidogenic conformational ensemble of the PI3K SH3 domain. Abstract Text:

Hee-Chul Ahn,Yen T H Le,Partha S Nagchowdhuri,Eugene F Derose,Cindy Putnam-Evans,Robert E London,John L Markley,Kwang Hun Lim,

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 degrees C) was shown to be substantially disordered with no secondary structural preferences. (15)N 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 degrees C). However, more restricted motions were detected in residues located primarily in the beta-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 long-range contacts between the dynamically restricted residues at the amyloid-forming condition.

NMR characterizations of an amyloidogenic conformational ensemble of the PI3K SH3 domain. Publishing Authors By Initials

HC Ahn,YT Le,PS Nagchowdhuri,EF Derose,C Putnam-Evans,RE London,JL Markley,KH Lim,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: molecular structure: molecular conformation: protein conformation: protein structure, tertiary: protein interaction domains and motifs: src homology domains research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: molecular structure: molecular conformation: protein conformation: protein structure, tertiary: protein interaction domains and motifs: src homology domains research

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NMR characterizations of an amyloidogenic conformational ensemble of the PI3K SH3 domain. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Protein science : a publication of the Protein Soc

VOLUME: 15

Page Numbers: 2552-7

Journal Abbreviation: Protein Sci.

ISSN: 0961-8368

DAY: 25

MONTH: 09

YEAR: 2006

NMR characterizations of an amyloidogenic conformational ensemble of the PI3K SH3 domain. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9211750

NMR characterizations of an amyloidogenic conformational ensemble of the PI3K SH3 domain. Keywords Mesh Terms:

KEYWORDS: src Homology Domains

MESH TERMS: methods

Chemical & Substance for Abstract: NMR characterizations of an amyloidogenic conformational ensemble of the PI3K SH3 domain. Information

Substance Name: 1-Phosphatidylinositol 3-Kinase

Registry Number: EC 2.7.1.137

Grant and Affiliation Information for NMR characterizations of an amyloidogenic conformational ensemble of the PI3K SH3 domain.

AFFILIATION: Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706-1544, USA.

Country: United States

AGENCY: United States NCRR

GRANT: P41RR02301

ACRONYM: RR

MEDLINETA: Protein Sci

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