2KKW

SLAS-micelle bound alpha-synuclein

Summary for 2KKW

• Entry DOI: 10.2210/pdb2kkw/pdb
• Descriptor: Alpha-synuclein (1 entity in total)
• Functional Keywords: protein-micelle interaction, lipid binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 14476.11

Authors

Rao, J.,Jao, C.C.,Hegde, B.,Langen, R.,Ulmer, T.S. (deposition date: 2009-06-29, release date: 2010-06-16, Last modification date: 2024-05-01)

Primary citation

Rao, J.N.,Jao, C.C.,Hegde, B.G.,Langen, R.,Ulmer, T.S.
A combinatorial NMR and EPR approach for evaluating the structural ensemble of partially folded proteins.
J.Am.Chem.Soc., 132:8657-8668, 2010

PubMed Abstract: Partially folded proteins, characterized as exhibiting secondary structure elements with loose or absent tertiary contacts, represent important intermediates in both physiological protein folding and pathological protein misfolding. To aid in the characterization of the structural state(s) of such proteins, a novel structure calculation scheme is presented that combines structural restraints derived from pulsed EPR and NMR spectroscopy. The methodology is established for the protein alpha-synuclein (alphaS), which exhibits characteristics of a partially folded protein when bound to a micelle of the detergent sodium lauroyl sarcosinate (SLAS). By combining 18 EPR-derived interelectron spin label distance distributions with NMR-based secondary structure definitions and bond vector restraints, interelectron distances were correlated and a set of theoretical ensemble basis populations was calculated. A minimal set of basis structures, representing the partially folded state of SLAS-bound alphaS, was subsequently derived by back-calculating correlated distance distributions. A surprising variety of well-defined protein-micelle interactions was thus revealed in which the micelle is engulfed by two differently arranged antiparallel alphaS helices. The methodology further provided the population ratios between dominant ensemble structural states, whereas limitation in obtainable structural resolution arose from spin label flexibility and residual uncertainties in secondary structure definitions. To advance the understanding of protein-micelle interactions, the present study concludes by showing that, in marked contrast to secondary structure stability, helix dynamics of SLAS-bound alphaS correlate with the degree of protein-induced departures from free micelle dimensions.

PubMed: 20524659
DOI: 10.1021/ja100646t

Experimental method

EPR
SOLUTION NMR