Molecular recognition of human islet amyloid polypeptide assembly by selective oligomerization of thioflavin T
Open Access
- 7 August 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 6 (32), eabc1449
- https://doi.org/10.1126/sciadv.abc1449
Abstract
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 hIAPP8–37 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 kBT, around 50% larger than that of the cohesive interaction between two side-by-side ThTs (4.2 kBT). 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.Keywords
Funding Information
- Natural Science Foundation of Shanghai (19ZR1412400)
- National Natural Science Foundation of China (31901007)
- Fundamental Research Funds for the Central Universities (2018PT31028)
- the CAMS Innovation Fund for Medical Sciences (2018-I2M-3-006)
- Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS (NSKF201812)
- State Key Laboratory Special Fund (2060204)
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