Single-molecule functional anatomy of endogenous HER2-HER3 heterodimers
- Authors
- Choi, Byoungsan; Cha, Minkwon; Bun, Gee Sung; Lee, Dae Hee; Lee, Seul; Ehsan, Muhammad; Chae, Pil Seok; Heo, Won Do; Park, YongKeun; Yoon, Tae-Young
- Issue Date
- Apr-2020
- Publisher
- ELIFE SCIENCES PUBLICATIONS LTD
- Citation
- ELIFE, v.9, pp.1 - 22
- Indexed
- SCIE
SCOPUS
- Journal Title
- ELIFE
- Volume
- 9
- Start Page
- 1
- End Page
- 22
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/1171
- DOI
- 10.7554/eLife.53934
- ISSN
- 2050-084X
- Abstract
- Human epidermal growth factor receptors (HERs) are the primary targets of many directed cancer therapies. However, the reason a specific dimer of HERs generates a stronger proliferative signal than other permutations remains unclear. Here, we used single-molecule immunoprecipitation to develop a biochemical assay for endogenously-formed, entire HER2-HER3 heterodimers. We observed unexpected, large conformational fluctuations in juxta-membrane and kinase domains of the HER2-HER3 heterodimer. Nevertheless, the individual HER2-HER3 heterodimers catalyze tyrosine phosphorylation at an unusually high rate, while simultaneously interacting with multiple copies of downstream signaling effectors. Our results suggest that the high catalytic rate and multi-tasking capability make a concerted contribution to the strong signaling potency of the HER2-HER3 heterodimers.
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Collections - COLLEGE OF ENGINEERING SCIENCES > DEPARTMENT OF BIONANO ENGINEERING > 1. Journal Articles
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