文献类型：期刊文献

英文题名：Molecular recognition of human islet amyloid polypeptide assembly by selective oligomerization of thioflavin T

作者：Yu, Lanlan[1,2];Zhang, Wenbo[1];Luo, Wendi[3,4];Dupont, Robert L.[5];Xu, Yang[5];Wang, Yibing[6];Tu, Bin[3];Xu, Haiyan[2];Wang, Xiaoguang[5];Fang, Qiaojun[3];Yang, Yanlian[3];Wang, Chen[3];Wang, Chenxuan[1]

机构：[1]Chinese Acad Med Sci & Peking Union Med Coll, Inst Basic Med Sci, State Key Lab Med Mol Biol, Beijing 100005, Peoples R China;[2]Chinese Acad Med Sci, Peking Union Med Coll, Sch Basic Med, Inst Basic Med Sci, Beijing 100005, Peoples R China;[3]Natl Ctr Nanosci & Technol, CAS Ctr Excellence Nanosci, CAS Key Lab Standardizat & Measurement Nanotechno, CAS Key Lab Biol Effects Nanomat & Nanosafety,Lab, Beijing 100190, Peoples R China;[4]Univ Chinese Acad Sci, Sino Danish Ctr Educ & Res, Beijing 100190, Peoples R China;[5]Ohio State Univ, William G Lowrie Dept Chem & Biomol Engn, Columbus, OH 43210 USA;[6]East China Univ Sci & Technol, Sch Biotechnol, State Key Lab Bioreactor Engn Biomed Nanotechnol, Shanghai Collaborat Innovat Ctr Biomfg Technol, Shanghai 200237, Peoples R China

年份：2020

卷号：6

期号：32

外文期刊名：SCIENCE ADVANCES

收录：;EI(收录号：20204009264070);WOS:【SCI-EXPANDED(收录号:WOS:000560452300035)】；

基金：C.W. thanks the CAMS Innovation Fund for Medical Sciences (2018-I2M-3-006), the National Natural Science Foundation of China (31901007), the Fundamental Research Funds for the Central Universities (2018PT31028), the Open Project Fund provided by the Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, the CAS (NSKF201812), the State Key Laboratory Special Fund 2060204, and the Natural Science Foundation of Shanghai (19ZR1412400). We also thank the National Center for Nanoscience and Technology, China, for STM facilities, and X. Mao (Johns Hopkins University) for discussion.

语种：英文

外文关键词：Adhesives - Probes - Glycoproteins - Neurodegenerative diseases - Molecules - Scanning tunneling microscopy - Oligomers - Proteins

摘要：Selective oligomerization is a common phenomenon existing widely in the formation of intricate biological structures in nature. The precise design of drug molecules with an oligomerization state that specifically recognizes its receptor, however, remains substantially challenging. Here, we used scanning tunneling microscopy (STM) to identify the oligomerization states of an amyloid probe thioflavin T (ThT) on hIAPP(8-37) assembly to be exclusively even numbers. We demonstrate that both adhesive interactions between ThT and the protein substrate and cohesive interactions among ThT molecules govern the oligomerization state of the bounded ThT. Specifically, the work of the cohesive interaction between two head/tail ThTs is determined to be 6.4 k(B)T, around 50% larger than that of the cohesive interaction between two side-by-side ThTs (4.2 k(B)T). Overall, our STM imaging and theoretical understanding at the single-molecule level provide valuable insights into the design of drug compounds using the selective oligomerization of molecular probes to recognize protein self-assembly.