Improved in situ characterization of protein complex dynamics at scale with thermal proximity co-aggregation

Sun，Siyuan1; Zheng，Zhenxiang1; Wang，Jun1; Li，Fengming1; He，An1; Lai，Kunjia1; Zhang，Shuang1,2; Lu，Jia Hong2; Tian，Ruijun1; Tan，Chris Soon Heng1

2023-12-01

10.1038/s41467-023-43526-2

Nature Communications   影响因子和分区

2041-1723

Cellular activities are carried out vastly by protein complexes but large repertoire of protein complexes remains functionally uncharacterized which necessitate new strategies to delineate their roles in various cellular processes and diseases. Thermal proximity co-aggregation (TPCA) is readily deployable to characterize protein complex dynamics in situ and at scale. We develop a version termed Slim-TPCA that uses fewer temperatures increasing throughputs by over 3X, with new scoring metrics and statistical evaluation that result in minimal compromise in coverage and detect more relevant complexes. Less samples are needed, batch effects are minimized while statistical evaluation cost is reduced by two orders of magnitude. We applied Slim-TPCA to profile K562 cells under different duration of glucose deprivation. More protein complexes are found dissociated, in accordance with the expected downregulation of most cellular activities, that include 55S ribosome and respiratory complexes in mitochondria revealing the utility of TPCA to study protein complexes in organelles. Protein complexes in protein transport and degradation are found increasingly assembled unveiling their involvement in metabolic reprogramming during glucose deprivation. In summary, Slim-TPCA is an efficient strategy for characterization of protein complexes at scale across cellular conditions, and is available as Python package at https://pypi.org/project/Slim-TPCA/ .

英语

NI论文

第一 ; 通讯

2-s2.0-85177801654

Scopus

1.Department of Chemistry and Research Center for Chemical Biology and Omics Analysis,College of Science,Southern University of Science and Technology,Shenzhen,Guangdong,China
2.State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macau,Zhuhai,SAR,Macao

Sun，Siyuan,Zheng，Zhenxiang,Wang，Jun,et al. Improved in situ characterization of protein complex dynamics at scale with thermal proximity co-aggregation[J]. Nature Communications,2023,14(1).

Sun，Siyuan.,Zheng，Zhenxiang.,Wang，Jun.,Li，Fengming.,He，An.,...&Tan，Chris Soon Heng.(2023).Improved in situ characterization of protein complex dynamics at scale with thermal proximity co-aggregation.Nature Communications,14(1).

Sun，Siyuan,et al."Improved in situ characterization of protein complex dynamics at scale with thermal proximity co-aggregation".Nature Communications 14.1(2023).