Structural analysis of the FERM domain of human protein tyrosine phosphatase non‐receptor type 21

• Published in: Acta crystallographica. Section F, Structural biology communications Structural biology communications, 2024-07, Vol.80 (7), p.148-153
• Main Authors: Lee, Hye Seon, Ku, Bonsu, Shin, Ho-Cheol, Kim, Seung Jun
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Binding Sites; cancer therapy; Crystal structure; Crystallography; Crystallography, X-Ray; FERM domains; Homology; Humans; Hydrophobic and Hydrophilic Interactions; Hydrophobicity; Kinesin; Models, Molecular; Protein Binding; Protein Domains; Protein folding; protein tyrosine phosphatase non‐receptor type 21; Protein Tyrosine Phosphatases, Non-Receptor - chemistry; Protein Tyrosine Phosphatases, Non-Receptor - genetics; Protein Tyrosine Phosphatases, Non-Receptor - metabolism; Protein-tyrosine-phosphatase; Proteins; protein‐binding selectivity; PTPN21; Receptors; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Structural analysis; Therapeutic targets; Tyrosine
• ISSN: 2053-230X; 2053-230X
• DOI: 10.1107/S2053230X24005260

Protein tyrosine phosphatase non‐receptor type 21 (PTPN21) is a cytosolic protein tyrosine phosphatase that regulates cell growth and invasion. Due to its oncogenic properties, PTPN21 has recently emerged as a potential therapeutic target for cancer. In this study, the three‐dimensional structure of the PTPN21 FERM domain was determined at 2.1 Å resolution by X‐ray crystallography. The crystal structure showed that this domain harbors canonical FERM folding and consists of three subdomains that are tightly packed via highly conserved intramolecular hydrophobic interactions. Consistent with this, the PTPN21 FERM domain shares high structural homology with several other FERM domains. Moreover, structural superimposition demonstrated two putative protein‐binding sites of the PTPN21 FERM domain, which are presumed to be associated with interaction with its binding partner, kinesin family member 1C. Thus, these data suggest that the FERM domain of PTPN21 serves as a module that mediates protein–protein interaction, like other FERM domains. The crystal structure of the FERM domain of protein tyrosine phosphatase non‐receptor type 21, a regulator of cancer progression and invasion, was determined and an atomic‐level structural analysis was conducted.