Alpha-synuclein tertiary contact dynamics.
Tertiary contact formation rates in alpha-synuclein, an intrinsically disordered polypeptide implicated in Parkinson's disease, have been determined from measurements of diffusion-limited electron-transfer kinetics between triplet-excited tryptophan:3-nitrotyrosine pairs separated by 10, 12, 55, and 90 residues. Calculations based on a Markovian lattice model developed to describe intrachain diffusion dynamics for a disordered polypeptide give contact quenching rates for various loop sizes ranging from 6 to 48 that are in reasonable agreement with experimentally determined values for small loops (10-20 residues). Contrary to expectations, measured contact rates in alpha-synuclein do not continue to decrease as the loop size increases (>/=35 residues), and substantial deviations from calculated rates are found for the pairs W4-Y94, Y39-W94, and W4-Y136. The contact rates for these large loops indicate much shorter average donor-acceptor separations than expected for a random polymer.
Lee
Jennifer C
JC
Laboratory of Molecular Biophysics, National Heart, Lung, and Blood Institute, National Institutes of Health, 50 South Drive, Bethesda, Maryland 20892, USA.
Lai
Bert T
BT
Kozak
John J
JJ
Gray
Harry B
HB
Winkler
Jay R
JR
D000595:Amino Acid Sequence; D004579:Electron Transport; D008969:Molecular Sequence Data; D011487:Protein Conformation; D014364:Tryptophan / Q000737:chemistry*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry; D051844:alpha-Synuclein / Q000737:chemistry*
D051844:alpha-Synuclein; C002744:3-nitrotyrosine; D014443:Tyrosine; D014364:Tryptophan