Discordant and chameleon sequences: Their distribution and implications for amyloidogenicity

作者：Gendoo Deena M A; Harrison Paul M^*

来源：Protein Science, 2011, 20(3): 567-579.

DOI：10.1002/pro.590

• discordance
• chameleon sequences
• amyloid fibril
• amyloidosis
• prion
• conformational variability
• bioinformatics
• beta-sheet
• structural plasticity
• structurally ambivalent peptides

Identification of ambiguous encoding in protein secondary structure is paramount to develop an understanding of key protein segments underlying amyloid diseases. We investigate two types of structurally ambivalent peptides, which were hypothesized in the literature as indicators of amyloidogenic proteins: discordant alpha-helices and chameleon sequences. Chameleon sequences are peptides discovered experimentally in different secondary-structure types. Discordant alpha-helices are alpha-helical stretches with strong beta-strand propensity or prediction. To assess the distribution of these features in known protein structures, and their potential role in amyloidogenesis, we analyzed the occurrence of discordant alpha-helices and chameleon sequences in nonredundant sets of protein domains (n = 4263) and amyloidogenic proteins extracted from the literature (n = 77). Discordant alpha-helices were identified if discordance was observed between known secondary structures and secondary-structure predictions from the GOR-IV and PSIPRED algorithms. Chameleon sequences were extracted by searching for identical sequence words in alpha-helices and beta-strands. We defined frustrated chameleons and very frustrated chameleons based on varying degrees of total beta propensity >=alpha propensity. To our knowledge, this is the first study to discern statistical relationships between discordance, chameleons, and amyloidogenicity. We observed varying enrichment levels for some categories of discordant and chameleon sequences in amyloidogenic sequences. Chameleon sequences are also significantly enriched in proteins that have discordant helices, indicating a clear link between both phenomena. We identified the first set of discordant-chameleonic protein segments we predict may be involved in amyloidosis. We present a detailed analysis of discordant and chameleons segments in the family of one of the amyloidogenic proteins, the Prion Protein.

• 出版日期2011-3
• 单位上海生物信息技术研究中心