The APOBEC3C crystal structure and the interface for HIV-1 Vif binding
| Autor: | Yuriko Naganawa, Shingo Kitamura, Nobuhisa Watanabe, Yasumasa Iwatani, Masaaki Nakashima, Takashi Yamane, Wataru Sugiura, Yoshiyuki Yokomaku, Hirotaka Ode, Atsuo Suzuki, Teppei Kurosawa, Mayumi Imahashi |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Protein Conformation viruses Biology Crystallography X-Ray Conserved sequence Cytosine Deaminase chemistry.chemical_compound Protein structure Structural Biology Cytidine Deaminase vif Gene Products Human Immunodeficiency Virus Humans Amino Acid Sequence Binding site Molecular Biology Peptide sequence APOBEC3G Conserved Sequence Binding Sites Virion virus diseases Cytidine Cytidine deaminase biochemical phenomena metabolism and nutrition Viral infectivity factor Cell biology Biochemistry chemistry HIV-1 Mutagenesis Site-Directed HeLa Cells |
| Zdroj: | Nature structuralmolecular biology. 19(10) |
| ISSN: | 1545-9985 |
| Popis: | The human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3, referred to as A3) proteins are cellular cytidine deaminases that potently restrict retrovirus replication. However, HIV-1 viral infectivity factor (Vif) counteracts the antiviral activity of most A3 proteins by targeting them for proteasomal degradation. To date, the structure of an A3 protein containing a Vif-binding interface has not been solved. Here, we report a high-resolution crystal structure of APOBEC3C and identify the HIV-1 Vif-interaction interface. Extensive structure-guided mutagenesis revealed the role of a shallow cavity composed of hydrophobic or negatively charged residues between the α2 and α3 helices. This region is distant from the DPD motif (residues 128-130) of APOBEC3G that participates in HIV-1 Vif interaction. These findings provide insight into Vif-A3 interactions and could lead to the development of new pharmacologic anti-HIV-1 compounds. |
| Databáze: | OpenAIRE |
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