Structural Insight on Functional Regulation of Human MINERVA Protein

International Journal of Molecular Sciences

Dong Man Jang¹  Byung Woo Han¹  Yeon Lee²  Hyoun Sook Kim²  Heesun Cheong²  Dong-Eun Lee²  Hyunggu Hahn²  Jiyoun Kim² 

[1] Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Korea;Research Institute, National Cancer Center, Goyang, Gyeonggi 10408, Korea;

关键词: MINERVA;    FAM129B;    PH domain;    lipid binding;    novel fold;    cancer progression;   

DOI  :  10.3390/ijms21218186

来源: DOAJ

【 摘 要 】

MINERVA (melanoma invasion by ERK), also known as FAM129B, is a member of the FAM129 protein family, which is only present in vertebrates. MINERVA is involved in key signaling pathways regulating cell survival, proliferation and apoptosis and found upregulated in many types of cancer promoting invasion. However, the exact function of the protein remains elusive. X-ray crystallographic methods were implemented to determine the crystal structure of MINERVA^ΔC, lacking C-terminal flexible region. Trypsin digestion was required before crystallization to obtain diffraction-quality crystals. While the N-terminal pleckstrin homology (PH) domain exhibits the typical fold of PH domains, lipid binding assay indicates specific affinity towards phosphatidic acid and inositol 3-phosphate. A helix-rich domain that constitutes the rest of the molecule demonstrates a novel L-shaped fold that encompasses the PH domain. The overall structure of MINERVA^ΔC with binding assays and cell-based experiments suggest plasma membrane association of MINERVA and its function seem to be tightly regulated by various motifs within the C-terminal flexible region. Elucidation of MINERVA^ΔC structure presents a novel fold for an α-helix bundle domain that would provide a binding platform for interacting partners.

【 授权许可】

Unknown