PTPMT1 (PTP localized to the Mitochondrion 1) is a member of the protein tyrosine phosphatase superfamily that is localized exclusively to the mitochondrion. We recently reported that PTPMT1 dephosphorylates phosphatidylglycerol phosphate, an essential intermediate of cardiolipin biosynthesis. To gain further insights into the molecular basis of PTPMT1 function, we determined the crystal structures of the phosphatase domain of PTPMT1. PTPMT1 exhibits a canonical protein tyrosine phosphatase domain fold, resembling many dual-specificity phosphatases such as phosphatase and tensin homolog and vaccinia H1-related phosphatase. We also determined the structure of the catalytically inactive phosphatase in complex with a surrogate substrate, phosphatidylinositol 5-phosphate, which sheds light on the substrate recognition and specificity of PTPMT1. Comparison of the apo and substrate-bound structures of PTPMT1 suggests that it undergoes significant conformational change during catalysis, and we further demonstrated that an evolutionarily conserved EEYE loop is important for its activity.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142007 | PMC |
http://dx.doi.org/10.1073/pnas.1109290108 | DOI Listing |
Transl Cancer Res
December 2024
Department of Medical Oncology, Qinghai Provincial People's Hospital, Xining, China.
Background: Many cancer cells exhibit aberrant metabolic reprogramming through abnormal mitochondrial respiration. Protein tyrosine phosphatase mitochondrial 1 (PTPMT1) is a protein tyrosine phosphatase localized to the mitochondria and linked to mitochondrial respiration. However, the expression and role of PTPMT1 in regulating the biological characteristics of small cell lung cancer (SCLC) has not yet been explored.
View Article and Find Full Text PDFInt J Mol Sci
September 2024
Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, 44, Wenhuaxi Road, Jinan 250012, China.
The pathogenesis of ocular diseases (ODs) remains unclear, although genome-wide association studies (GWAS) have identified numerous associated genetic risk loci. We integrated protein quantitative trait loci (pQTL) datasets and five large-scale GWAS summary statistics of ODs under a cutting-edge systematic analytic framework. Proteome-wide association studies (PWAS) identified plasma and brain proteins associated with ODs, and 11 plasma proteins were identified by Mendelian randomization (MR) and colocalization (COLOC) analyses as being potentially causally associated with ODs.
View Article and Find Full Text PDFJ Transl Med
October 2024
Medical School of Chinese People's Liberation Army, 28 Fuxing Road, 100853, Beijing, China.
Brain
August 2024
Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK.
Primary mitochondrial diseases (PMDs) are among the most common inherited neurological disorders. They are caused by pathogenic variants in mitochondrial or nuclear DNA that disrupt mitochondrial structure and/or function, leading to impaired oxidative phosphorylation (OXPHOS). One emerging subcategory of PMDs involves defective phospholipid (PL) metabolism.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Cell Res
December 2024
MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, State Key Laboratory of Oncology in Southern China, Sun Yat-sen University, Guangzhou 510275, PR China; Key Laboratory of Liver Disease of Guangdong Province, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, PR China. Electronic address:
The role of micropeptide in cardiomyocyte proliferation remains unknown. We found that MPM (micropeptide in mitochondria) was highly expressed in cardiomyocytes. Compared to MPM mice, MPM knockout (MPM) mice exhibited reduction in left ventricular (LV) mass, myocardial thickness and LV fractional shortening.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!