An unstructured region is required by GAV homologue for the fibrillization of host proteins.
Accumulating evidence shows that some amyloidogenic proteins contain core sequences, which are critical for their fibrillization. Core sequences of alpha-synuclein, beta-amyloid peptide and prion protein usually reside in their unfolded regions and share a conserved consensus (VGGAVVAGV) designated as GAV homologue. Here we investigate the role of unfolded regions in fibrillization after GAV homologue is attached to the C-terminus or inserted into the loop regions of different host proteins, namely alpha -Syn1-65, gamma-synuclein, E. coli thioredoxin and immunoglobulin G binding B1 domain of streptococcal protein G. The results imply that an unstructured region is required by GAV homologue for the fibrillization of host proteins. A number of amyloidogenic proteins with core sequences located in unstructured regions are summarized and discussed in details. The finding may provide further insight into the elucidating of the molecular mechanism underlying the fibrillization of alpha-Syn, Abeta and PrP as well as other amyloidogenic proteins.
Ji
Li-Na
LN
Key Laboratory of Proteomics, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, P.R. China.
Du
Hai-Ning
HN
Zhang
Feng
F
Li
Hong-Tao
HT
Luo
Xiao-Ying
XY
Hu
Jun
J
Hu
Hong-Yu
HY
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D017124:Conserved Sequence / Q000502:physiology*; D006801:Humans; D011328:Prions / Q000737:chemistry*; D017433:Protein Structure, Secondary; D051844:alpha-Synuclein / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D011328:Prions; D051844:alpha-Synuclein