title: Molecular Analysis of AFP and HSA Interactions with PTEN Protein.
abstract: Human cytoplasmic alpha-fetoprotein (AFP) has been classified as a member of the albuminoid gene family. The protein sequence of AFP has significant homology to that of human serum albumin (HSA), but its biological characteristics are vastly different from HSA. The AFP functions as a regulator in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway, but HSA plays a key role as a transport protein. To probe their molecular mechanisms, we have applied colocalization, coimmunoprecipitation (co-IP), and molecular docking approaches to analyze the differences between AFP and HSA. The data from colocalization and co-IP displayed a strong interaction between AFP and PTEN (phosphatase and tensin homolog), demonstrating that AFP did bind to PTEN, but HSA did not. The molecular docking study further showed that the AFP domains I and III could contact with PTEN. In silicon substitutions of AFP binding site residues at position 490M/K and 105L/R corresponding to residues K490 and R105 in HSA resulted in steric clashes with PTEN residues R150 and K46, respectively. These steric clashes may explain the reason why HSA cannot bind to PTEN. Ultimately, the experimental results and the molecular modeling data from the interactions of AFP and HSA with PTEN will help us to identify targets for designing drugs and vaccines against human hepatocellular carcinoma.
authors.affiliation: College of Agriculture, Hainan University, Haikou, Hainan 570228, China ; Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College, Haikou, Hainan 571199, China.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College, Haikou, Hainan 571199, China ; Key Laboratory of Molecular Biology, Hainan Medical College, Haikou, Hainan 571199, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Lin
authors.affiliation: College of Agriculture, Hainan University, Haikou, Hainan 570228, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.affiliation: College of Agriculture, Hainan University, Haikou, Hainan 570228, China ; Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College, Haikou, Hainan 571199, China ; Key Laboratory of Molecular Biology, Hainan Medical College, Haikou, Hainan 571199, China ; Institution of Tumor, Hainan Medical College, Haikou, Hainan 570102, China.
authors.forename: Mengsen
authors.initials: M
authors.lastname: Li
mesh_terms: D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D062105:Molecular Docking Simulation; D051059:PTEN Phosphohydrolase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D012709:Serum Albumin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D000509:alpha-Fetoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C097353:AFP protein, human; D012709:Serum Albumin; D000509:alpha-Fetoproteins; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human