Spider Silk Protein Forms Amyloid-Like Nanofibrils through a Non-Nucleation-Dependent Polymerization Mechanism

作者全名："Qi, Xingmei; Wang, Yu; Yu, Hairui; Liu, Ruifang; Leppert, Axel; Zheng, Zihan; Zhong, Xueying; Jin, Zhen; Wang, Han; Li, Xiaoli; Wang, Xiuzhe; Landreh, Michael; Morozova-Roche, Ludmilla A.; Johansson, Jan; Xiong, Sidong; Iashchishyn, Igor; Chen, Gefei"

作者地址："[Qi, Xingmei; Yu, Hairui; Liu, Ruifang; Wang, Han; Xiong, Sidong] Soochow Univ, Inst Biol, Jiangsu Key Lab Infect & Immun, Suzhou 215123, Peoples R China; [Qi, Xingmei; Yu, Hairui; Liu, Ruifang; Wang, Han; Xiong, Sidong] Soochow Univ, Inst Med Sci, Jiangsu Key Lab Infect & Immun, Suzhou 215123, Peoples R China; [Wang, Yu; Zheng, Zihan; Jin, Zhen; Johansson, Jan; Chen, Gefei] Karolinska Inst, Dept Biosci & Nutr, S-14157 Huddinge, Sweden; [Wang, Yu] Northeast Forestry Univ, Coll Wildlife & Protected Area, Harbin 150040, Peoples R China; [Leppert, Axel; Landreh, Michael] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17165 Solna, Sweden; [Zheng, Zihan; Jin, Zhen] Xi An Jiao Tong Univ, Dept Pharmacol, Xian 710061, Shaanxi, Peoples R China; [Zhong, Xueying] KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Biomed Engn & Hlth Syst, S-14152 Huddinge, Sweden; [Li, Xiaoli] Chongqing Med Univ, Coll Pharm, Dept Pharmacol, Chongqing 400016, Peoples R China; [Wang, Xiuzhe] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 6, Sch Med, Dept Neurol, Shanghai 200233, Peoples R China; [Morozova-Roche, Ludmilla A.; Iashchishyn, Igor] Umea Univ, Dept Med Biochem & Biophys, S-90187 Umea, Sweden"

通信作者："Chen, GF (通讯作者)，Karolinska Inst, Dept Biosci & Nutr, S-14157 Huddinge, Sweden."

来源：SMALL

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:001029348000001

JCR分区：Q1

影响因子：13

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：cytotoxicity; nanofibril; non-nucleation-dependent polymerization; seeding; spidroin

摘要："Amyloid fibrils-nanoscale fibrillar aggregates with high levels of order-are pathogenic in some today incurable human diseases; however, there are also many physiologically functioning amyloids in nature. The process of amyloid formation is typically nucleation-elongation-dependent, as exemplified by the pathogenic amyloid-& beta; peptide (A & beta;) that is associated with Alzheimer's disease. Spider silk, one of the toughest biomaterials, shares characteristics with amyloid. In this study, it is shown that forming amyloid-like nanofibrils is an inherent property preserved by various spider silk proteins (spidroins). Both spidroins and A & beta; capped by spidroin N- and C-terminal domains, can assemble into macroscopic spider silk-like fibers that consist of straight nanofibrils parallel to the fiber axis as observed in native spider silk. While A & beta; forms amyloid nanofibrils through a nucleation-dependent pathway and exhibits strong cytotoxicity and seeding effects, spidroins spontaneously and rapidly form amyloid-like nanofibrils via a non-nucleation-dependent polymerization pathway that involves lateral packing of fibrils. Spidroin nanofibrils share amyloid-like properties but lack strong cytotoxicity and the ability to self-seed or cross-seed human amyloidogenic peptides. These results suggest that spidroins & PRIME; unique primary structures have evolved to allow functional properties of amyloid, and at the same time direct their fibrillization pathways to avoid formation of cytotoxic intermediates."

基金机构：National Nature Science Foundation of China [31771003]; Alzheimer's Association Research Grant; Olle Engkvists Stiftelse; Petrus and Augusta Hedlunds Stiftelse; ke Wibergs stiftelse; Swedish Alzheimer foundation; Karolinska Institutet Research Foundation; Stiftelsen fouml;r Gamla Tjauml;narinnor; Stiftelsen Sigurd och Elsa Goljes Minne; Loo and Hans Osterman Foundation; Geriatric Diseases Foundation at Karolinska Institutet; Gun and Bertil Stohne's Foundation; Magnus Bergvall foundation; China Scholarship Council; China Association for Science and Technology

基金资助正文："X.Q. and Y.W. contributed equally to this work. This study was supported by the National Nature Science Foundation of China (No. 31771003. G.C. is supported by the Alzheimer's Association Research Grant, Olle Engkvists Stiftelse, the Petrus and Augusta Hedlunds Stiftelse, ake Wibergs stiftelse, the Swedish Alzheimer foundation, the ahlen Stiftelsens, Karolinska Institutet Research Foundation Grant, the Stiftelsen foer Gamla Tjaenarinnor, the Stiftelsen Sigurd och Elsa Goljes Minne, the Loo and Hans Osterman Foundation, Geriatric Diseases Foundation at Karolinska Institutet, the Gun and Bertil Stohne's Foundation and the Magnus Bergvall foundation. X.Z., Z.J., and Z.Z. are supported by the China Scholarship Council. Y.W. is supported by the China Association for Science and Technology."