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SHP-1 tyrosine phosphatase binding to c-Src kinase phosphor-dependent conformations: A comparative structural
Mehreen Gul1, Ahmad Navid1, Muhammad Fakhar1
1National Center for Bioinformatics, Quaid-i-Azam University, Islamabad, Pakistan.
Plos One
|January 13, 2023
Summary
The study reveals how SHP-1 (SH2-containing protein tyrosine phosphatase 1) binds to c-Src (a non-receptor tyrosine kinase) in its active and inactive forms. This interaction is key for understanding cancer development and potential therapies.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- SHP-1 is a tyrosine phosphatase in hematopoietic cells, regulating signaling pathways crucial for cancer.
- c-Src is a kinase involved in various cellular functions and cancer pathogenesis.
Purpose of the Study:
- To investigate the binding preferences of SHP-1 to both active (open) and inactive (closed) forms of c-Src using in silico methods.
- To elucidate the molecular interactions and conformational changes involved in SHP-1 and c-Src binding.
Main Methods:
- In silico approaches, including molecular dynamics simulations.
- Dynamic correlation analysis to assess domain interactions.
Main Results:
- SHP-1 binding induces greater conformational changes in inactive c-Src compared to active c-Src.
- Specific loops (WPD and Q) of SHP-1's PTP domain mediate binding to inactive c-Src's C-terminal tail.
- Distinct domain correlations were observed between SHP-1 and active versus inactive c-Src.
Conclusions:
- SHP-1 binding to c-Src involves specific intermolecular interactions and conformational readjustments.
- Understanding these interactions is crucial for developing targeted cancer therapies by modulating SHP-1/c-Src signaling.
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