A maximum entropy approach to the study of residue-specific backbone angle distributions in alpha-synuclein, an intrinsically disordered protein

作者：Mantsyzov Alexey B; Maltsev Alexander S; Ying Jinfa; Shen Yang; Hummer Gerhard; Bax Ad^*

来源：Protein Science, 2014, 23(9): 1275-1290.

DOI：10.1002/pro.2511

• diffusion anisotropy
• intrinsically disordered proteins
• Karplus curve
• random coil
• short-range NOE

alpha-Synuclein is an intrinsically disordered protein of 140 residues that switches to an alpha-helical conformation upon binding phospholipid membranes. We characterize its residue-specific backbone structure in free solution with a novel maximum entropy procedure that integrates an extensive set of NMR data. These data include intraresidue and sequential H-N-H-alpha and H-N-H-N NOEs, values for (3)J(HNH alpha), (1)J(H alpha C alpha), (2)J(C alpha N), and (1)J(C alpha N), as well as chemical shifts of N-15, C-13(alpha), and C-13' nuclei, which are sensitive to backbone torsion angles. Distributions of these torsion angles were identified that yield best agreement to the experimental data, while using an entropy term to minimize the deviation from statistical distributions seen in a large protein coil library. Results indicate that although at the individual residue level considerable deviations from the coil library distribution are seen, on average the fitted distributions agree fairly well with this library, yielding a moderate population (20-30%) of the PPII region and a somewhat higher population of the potentially aggregation-prone beta region (20-40%) than seen in the database. A generally lower population of the alpha(R) region (10-20%) is found. Analysis of H-1-H-1 NOE data required consideration of the considerable backbone diffusion anisotropy of a disordered protein.

• 出版日期2014-9
• 单位NIH