Identification of Protein Direct Interactome with Genetic Code Expansion and Search Engine OpenUaa
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Identification of Protein Direct Interactome with Genetic Code Expansion and Search Engine OpenUaa. / Liu, Chao; Wu, Ting; Shu, Xin; Li, Shang-Tong; Wang, Daniel R.; Wang, Nanxi; Zhou, Rong; Yang, Hao; Jiang, Hong; Hendriks, Ivo A.; Gong, Pengyun; Zhang, Long; Nielsen, Michael L.; Li, Kui; Wang, Lei; Yang, Bing.
In: Advanced Biology, Vol. 5, No. 3, 2000308, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Identification of Protein Direct Interactome with Genetic Code Expansion and Search Engine OpenUaa
AU - Liu, Chao
AU - Wu, Ting
AU - Shu, Xin
AU - Li, Shang-Tong
AU - Wang, Daniel R.
AU - Wang, Nanxi
AU - Zhou, Rong
AU - Yang, Hao
AU - Jiang, Hong
AU - Hendriks, Ivo A.
AU - Gong, Pengyun
AU - Zhang, Long
AU - Nielsen, Michael L.
AU - Li, Kui
AU - Wang, Lei
AU - Yang, Bing
PY - 2021
Y1 - 2021
N2 - Protein crosslinks occur endogenously such as modifications by ubiquitin-like proteins for signaling, or exogenously through genetically encoded chemical crosslinkers (GECX) for studying elusive protein-protein interactions. However, it remains challenging to identify these protein crosslinks efficiently at the proteomic scale. Herein, software OpenUaa is developed for identifying protein crosslinks generated by genetically encoded unnatural amino acids and endogenous protein conjugation. OpenUaa features inclusive and open search capability, dramatically improving identification sensitivity and coverage. Integrating GECX with OpenUaa, the direct interactome of thioredoxin is identified in Escherichia coli cells, yielding 289 crosslinked peptides and corresponding to 205 direct binding protein of thioredoxin. These identified direct binders provide evidence for thioredoxin's regulation of redox state and mitochondria energy metabolism. When identifying endogenous conjugation of small ubiquitin-like modifier (SUMO), OpenUaa also markedly improves coverage of SUMOylated peptides by ≈92%, revealing new SUMO targets. GECX-OpenUaa will enable efficient identification of direct interactomes of various proteins in live cells.
AB - Protein crosslinks occur endogenously such as modifications by ubiquitin-like proteins for signaling, or exogenously through genetically encoded chemical crosslinkers (GECX) for studying elusive protein-protein interactions. However, it remains challenging to identify these protein crosslinks efficiently at the proteomic scale. Herein, software OpenUaa is developed for identifying protein crosslinks generated by genetically encoded unnatural amino acids and endogenous protein conjugation. OpenUaa features inclusive and open search capability, dramatically improving identification sensitivity and coverage. Integrating GECX with OpenUaa, the direct interactome of thioredoxin is identified in Escherichia coli cells, yielding 289 crosslinked peptides and corresponding to 205 direct binding protein of thioredoxin. These identified direct binders provide evidence for thioredoxin's regulation of redox state and mitochondria energy metabolism. When identifying endogenous conjugation of small ubiquitin-like modifier (SUMO), OpenUaa also markedly improves coverage of SUMOylated peptides by ≈92%, revealing new SUMO targets. GECX-OpenUaa will enable efficient identification of direct interactomes of various proteins in live cells.
U2 - 10.1002/adbi.202000308
DO - 10.1002/adbi.202000308
M3 - Journal article
C2 - 33729691
VL - 5
JO - Advanced Biology
JF - Advanced Biology
SN - 2701-0198
IS - 3
M1 - 2000308
ER -
ID: 259630879