The characterization and comparison of amyloidogenic segments and non-amyloidogenic segments shed light on amyloid formation.
Amyloid fibrillar aggregates of proteins or peptides are involved in the etiology of several neurodegenerative diseases and represent a major problem in healthcare. Short regions in the protein trigger this aggregation. It is important to understand the basis of such short regions aggregation and amyloidosis for therapeutic intervention. In this study, we describe specific physico-chemical properties of amyloidogenic segments and compare them with non-amyloidogenic segments. First, amyloidogenic segments are characterized by lower values for average net charge, electrostatic potential, solvent accessible surface area and B-factor when compared to the non-amyloidogenic segments of the same proteins. Second, they are enriched in hydrophobic residues and have a tendency to form hydrogen bonds. Thus, amyloidogenic segments have distinct physico-chemical properties that are different from those of non-amyloidogenic segments. Third, and quite unexpectedly, our dynamic simulation studies support the hypothesis that amyloidogenic segments have lower average flexibility than non-amyloidogenic segments. Furthermore, the presence of amyloidogenic segments in disordered proteins does not contradict the observation that amyloidogenic segments are less flexible.
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, 32, Eastern Jiaochang Road, Kunming, Yunnan 650223, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China.
Shunmei
S
Chen
Boyce Thompson Institute for Plant Research, Cornell University, Ithaca, NY 14853, USA.
Shan
S
Gao
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, 32, Eastern Jiaochang Road, Kunming, Yunnan 650223, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China.
Dongqiang
D
Cheng
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, 32, Eastern Jiaochang Road, Kunming, Yunnan 650223, China; Kunming Institute of Zoology - Chinese University of Hongkong Joint Research Center for Bio-Resources and Human Disease Mechanisms, Kunming 650223, China. Electronic address: huangjf@mail.kiz.ac.cn.
Jingfei
J
Huang
D000682:Amyloid / Q000096:biosynthesis* / Q000737:chemistry*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation
D000682:Amyloid
Amyloid; Amyloidogenic segments; Flexibility; Non-amyloidogenic segments; Physico-chemical properties