Premium
Structural characterization and directed modification of Sus scrofa SAMHD 1 reveal the mechanism underlying deoxynucleotide regulation
Author(s) -
Kong Jia,
Wang Meimei,
He Shuangyi,
Peng Xin,
Qin Xiaohong
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14943
Subject(s) - tetramer , mutagenesis , enzyme , biology , biochemistry , protein structure , histidine , chemistry , computational biology , microbiology and biotechnology , mutation , gene
Sterile α‐motif/histidine–aspartate domain‐containing protein 1 ( SAMHD 1) is an intrinsic antiviral restriction factor known to play a vital role in preventing multiple viral infections and in the control of the cellular deoxynucleoside triphosphate ( dNTP ) pool. Human and mouse SAMHD 1 have both been extensively studied; however, our knowledge on porcine SAMHD 1 is limited. Here, we report our findings from comprehensive structural and functional studies on porcine SAMHD 1. We determined the crystal structure of porcine SAMHD 1 and showed that it forms a symmetric tetramer. Moreover, we modified the deoxynucleotide triphosphohydrolase ( dNTP ase) activity of SAMHD 1 by site‐directed mutagenesis based on the crystal structure, and obtained an artificial dimeric enzyme possessing high dNTP ase activity. Taken together, our results define the mechanism underlying dNTP regulation and provide a deeper understanding of the regulation of porcine SAMHD 1 functions. Directed modification of key residues based on the protein structure enhances the activity of the enzyme, which will be beneficial in the search for new antiviral strategies and for future translational applications.