Refinement of under-determined loops of Human Prion Protein by database-derived distance constraints.
Due to insufficient experimental restraints, a biologically critical loop region in PrP(c) (residues 167-171), which is a potential binding site for Protein X, is under-determined in most mammalian species. Here, we show that by adding information about distance constraints derived from a database of high-resolution protein structures, this under-determined loop as well as other secondary structural elements of the E200K variant of Human Prion Protein (hPrP(c)), a disease-related isoform, can be refined into more realistic structures in the structural ensemble with improved quality and increased accuracy. In particular, the ensemble becomes more compact after the refinement and the percentage of residues in the most favourable region of the Ramachandran diagram is increased to about 90% in the refined structures from the 80% to 85% range in the previously reported structures.
Cui
Feng
F
Program on Bioinformatics and Computational Biology, Iowa State University, Ames, Iowa 50011, USA. cuif@mail.nih.edu
Mukhopadhyay
Kriti
K
Young
Won-Bin
WB
Jernigan
Robert L
RL
Wu
Zhijun
Z
D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D006801:Humans; D018621:PrPC Proteins / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding
D018621:PrPC Proteins