8GXE

PTPN21 FERM PTP complex

8GXE の概要

• エントリーDOI: 10.2210/pdb8gxe/pdb
• 分子名称: Tyrosine-protein phosphatase non-receptor type 21, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: ptpn21, ferm, phosphotase domain, ptp, ptpd1, hydrolase, protein binding- hydrolase complex, protein binding/ hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68460.11

構造登録者

Chen, L.,Zheng, Y.Y.,Zhou, C. (登録日: 2022-09-19, 公開日: 2023-09-27, 最終更新日: 2024-04-17)

主引用文献

Chen, L.,Qian, Z.,Zheng, Y.,Zhang, J.,Sun, J.,Zhou, C.,Xiao, H.
Structural analysis of PTPN21 reveals a dominant-negative effect of the FERM domain on its phosphatase activity.
Sci Adv, 10:eadi7404-eadi7404, 2024

PubMed Abstract: PTPN21 belongs to the four-point-one, ezrin, radixin, moesin (FERM) domain-containing protein tyrosine phosphatases (PTP) and plays important roles in cytoskeleton-associated cellular processes like cell adhesion, motility, and cargo transport. Because of the presence of a WPE loop instead of a WPD loop in the phosphatase domain, it is often considered to lack phosphatase activity. However, many of PTPN21's biological functions require its catalytic activity. To reconcile these findings, we have determined the structures of individual PTPN21 FERM, PTP domains, and a complex between FERM-PTP. Combined with biochemical analysis, we have found that PTPN21 PTP is weakly active and is autoinhibited by association with its FERM domain. Disruption of FERM-PTP interaction results in enhanced ERK activation. The oncogenic HPV18 E7 protein binds to PTP at the same location as PTPN21 FERM, indicating that it may act by displacing the FERM domain from PTP. Our results provide mechanistic insight into PTPN21 and benefit functional studies of PTPN21-mediated processes.

PubMed: 38416831
DOI: 10.1126/sciadv.adi7404

実験手法

X-RAY DIFFRACTION (3 Å)