https://scholars.lib.ntu.edu.tw/handle/123456789/503208
標題: | Membrane protein assembly: Two cytoplasmic phosphorylated serine sites of Vpu from HIV-1 affect oligomerization | 作者: | Chen, C.-P. Lin, M.-H. Chan, Y.-T. Chen, L.-C. Ma, C. Fischer, W.B. |
公開日期: | 2016 | 出版社: | Nature Publishing Group | 卷: | 6 | 期: | 28866 | 起(迄)頁: | 1-13 | 來源出版物: | Scientific Reports | 摘要: | Viral protein U (Vpu) encoded by human immunodeficiency virus type 1 (HIV-1) is a short integral membrane protein which is known to self-assemble within the lipid membrane and associate with host factors during the HIV-1 infectivity cycle. In this study, full-length Vpu (M group) from clone NL4-3 was over-expressed in human cells and purified in an oligomeric state. Various single and double mutations were constructed on its phosphorylation sites to mimic different degrees of phosphorylation. Size exclusion chromatography of wild-type Vpu and mutants indicated that the smallest assembly unit of Vpu was a dimer and over time Vpu formed higher oligomers. The rate of oligomerization increased when (i) the degree of phosphorylation at serines 52 and 56 was decreased and (ii) when the ionic strength was increased indicating that the cytoplasmic domain of Vpu affects oligomerization. Coarse-grained molecular dynamic simulations with models of wild-type and mutant Vpu in a hydrated lipid bilayer supported the experimental data in demonstrating that, in addition to a previously known role in downregulation of host factors, the phosphorylation sites of Vpu also modulate oligomerization. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/503208 | ISSN: | 20452322 | DOI: | 10.1038/srep28866 | SDG/關鍵字: | Human immunodeficiency virus protein; serine; viral protein; vpu protein, Human immunodeficiency virus 1; amino acid sequence; chemistry; HEK293 cell line; human; Human immunodeficiency virus 1; metabolism; molecular dynamics; phosphorylation; protein multimerization; protein processing; protein quaternary structure; Amino Acid Sequence; HEK293 Cells; HIV-1; Human Immunodeficiency Virus Proteins; Humans; Molecular Dynamics Simulation; Phosphorylation; Protein Multimerization; Protein Processing, Post-Translational; Protein Structure, Quaternary; Serine; Viral Regulatory and Accessory Proteins |
顯示於: | 凝態科學研究中心 |
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