Polyphosphate-dependent protein aggregation and its biological significance

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19224
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Osaka University
• Principal Investigator: Goto Yuji 大阪大学, 大学院工学研究科, 特任研究員 (40153770)
• Co-Investigator(Kenkyū-buntansha): 八木 寿梓 鳥取大学, 工学研究科, 准教授 (10432494)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 蛋白質 / 生体分子 / 老化 / 蛋白質凝集 / アミロイド線維 / 過飽和 / 溶解度 / 相転移

Outline of Final Research Achievements

Polyphosphate (polyP), consisting of up to 1,000 phosphoanhydride bond-linked phosphate monomers, is one of the most ancient, enigmatic, and negatively charged molecules in biology. Because polyP is present all around us, from cellular components to food additives, clarifying its effects and consequent biological roles will be important to further advance our understanding of amyloid fibrils and related topics. We studied the effects of polyP on amyloid fibril formation of beta2-microblobulin and alpha-synuclein and showed that amyloid fibril formation of both beta2-microblobulin and alpha-synuclein could be accelerated by counter anion-binding and preferential hydration at relatively lower and higher concentrations of polyP, respectively, depending on the chain length of polyP. On the other hand, although we challenged to prepare antibodies specific to polyP, we could not achieve the goal because the preparation of protein antigens with polyP attached was difficult.

Free Research Field

蛋白質科学

Academic Significance and Societal Importance of the Research Achievements

ポリリン酸は無味無臭で強い保水効果をもつことから、食品、飲料に添加されている。他方、リン酸が高度に重合したポリリン酸は、蛋白質凝集、アミロイド線維形成を強く促進するなど、生命機能における意義や、食品添加物としての妥当性に懸念がある。本研究は、これらを追求するものであり、ポリリン酸の効果やその作用機構の基盤を明らかにすることができた。本研究の成果をもとにさらに生命機能における意義や、食品添加物としての妥当性をさらに追及することができれば、より安全で安心な社会の構築につながると期待できる。