Structural highlights
Publication Abstract from PubMedThe T-cell protein tyrosine phosphatase (TCPTP/PTPN2) targets a broad variety of substrates across different subcellular compartments. In spite of that, the structural basis for the regulation of TCPTP's activity remains elusive. Here, we investigated whether the activity of TCPTP is regulated by a potential allosteric site in a comparable manner to its most similar PTP family member (PTP1B/PTPN1). We determined two crystal structures of TCPTP at 1.7 and 1.9 A resolutions that include helix alpha7 at the TCPTP C-terminus. Helix alpha7 has been functionally characterized in PTP1B and was identified as its allosteric switch. However, its function is unknown in TCPTP. Here, we demonstrate that truncation or deletion of helix alpha7 reduced the catalytic efficiency of TCPTP by approximately 4-fold. Collectively, our data supports an allosteric role of helix alpha7 in regulation of TCPTP's activity, similar to its function in PTP1B, and highlights that the coordination of helix alpha7 with the core catalytic domain is essential for the efficient catalytic function of TCPTP. Crystal Structure of TCPTP Unravels an Allosteric Regulatory Role of Helix alpha7 in Phosphatase Activity.,Singh JP, Lin MJ, Hsu SF, Peti W, Lee CC, Meng TC Biochemistry. 2021 Dec 28;60(51):3856-3867. doi: 10.1021/acs.biochem.1c00519., Epub 2021 Dec 15. PMID:34910875[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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