title: HD domain of SAMHD1 influences Vpx-induced degradation at a post-interaction step.
abstract: Primate SAMHD1 proteins are potent inhibitors of viruses, including retroviruses such as HIV-1, HIV-2, and SIV. Vpx, a distinctive viral protein expressed by HIV-2 and some SIVs, induces SAMHD1 degradation by forming a Vpx-DCAF1-based ubiquitin ligase complex. Either the N- or the C-terminus of SAMHD1 is critical for Vpx-induced degradation, depending on the types of SAMHD1 and Vpx proteins. However, it was not fully understood whether other regions of SAMHD1 also contribute to its depletion by Vpx. In the present study, we report that SAMHD1 from chicken (SAMHD1GG) was not degraded by SIVmac Vpx, in contrast with results for human SAMHD1 (SAMHD1HS). Results regarding to SAMHD1HS and SAMHD1GG fusion proteins supported previous findings that the C-terminus of SAMHD1HS is essential for Vpx-induced degradation. Internal domain substitution, however, revealed that the HD domain also contributes to Vpx-mediated SAMHD1 degradation. Interestingly, the HD domain influenced Vpx-mediated SAMHD1 degradation without affecting Vpx-SAMHD1 interaction. Therefore, our findings revealed that factors in addition to Vpx-SAMHD1 binding influence the efficiency of Vpx-mediated SAMHD1 degradation.
authors.affiliation: Institute of Virology and AIDS Research, First Hospital of Jilin University, Changchun, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
authors.affiliation: Institute of Virology and AIDS Research, First Hospital of Jilin University, Changchun, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Hou
authors.affiliation: Institute of Virology and AIDS Research, First Hospital of Jilin University, Changchun, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Institute of Virology and AIDS Research, First Hospital of Jilin University, Changchun, China.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Yu
authors.affiliation: Institute of Virology and AIDS Research, First Hospital of Jilin University, Changchun, China. Electronic address: jdu@jlu.edu.cn.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
mesh_terms: D000818:Animals; D001665:Binding Sites; D002645:Chickens; D057809:HEK293 Cells; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism* / Q000648:ultrastructure*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D000076106:SAM Domain and HD Domain-Containing Protein 1; D013329:Structure-Activity Relationship; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: C074286:VPX protein, Human immunodeficiency virus 2; D054334:Viral Regulatory and Accessory Proteins; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D046988:Proteasome Endopeptidase Complex; D020559:Monomeric GTP-Binding Proteins
keywords: HD domain; SAMHD1; Virus-induced proteasomal degradation; Virus–host interaction; Vpx