関連する実験動画

Updated: May 1, 2026

Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding

Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding

Published on: September 16, 2010

HIV-1制限因子のDNAデアミナーゼドメインの構造 APOBEC3G

Kuan-Ming Chen¹, Elena Harjes, Phillip J Gross

¹Department of Biochemistry, Molecular Biology and Biophysics, [of Minnesota, Minneapolis, Minnesota 55455, USA.

|February 22, 2008

まとめ

抗ウイルス酵素であるヒトのAPOBEC3Gタンパク質は,新しく決定された構造を持っています. この構造は,HIV-1のようなウイルスを抑制するためにDNAを結合する方法を示しています.

科学分野:

バイオケミストリーバイオケミストリー
構造生物学構造生物学とは
ウイルス学ウイルス学ウイルス学

背景:

APOBEC3G (アポリプロテインBメッセンジャー-RNA編集酵素,触媒ポリペプチドのような3G) は,HIV-1のようなレトロウイルスに対する抗ウイルス特性を持つヒトDNAデアミナーゼです.
その抗ウイルス活動は,HIV-1 Vifなどのウイルス因子によってしばしば克服され,APOBEC3Gの劣化につながります.
APOBEC3Gは,APOBEC1とAIDを含むポリヌクレオチド・サイトシン・デアミナーゼの一族に属し,それらは生理学的役割が異なっている.

研究の目的:

人間のAPOBEC3G触媒ドメインの溶液構造を決定する.
APOBEC3GによるDNA結合と触媒のメカニズムを解明する.
HIV-1 Vif.のようなウイルスタンパク質とのAPOBEC3Gの相互作用に関する洞察を提供するためです.

主な方法:

溶液構造の決定のための核磁気共鳴 (NMR) スペクトロスコーピー.
NMRを用いたDNAタイトレーション実験.
計算モデリング.
フィロジェネティック保存分析.
エシェリキア・コライベースの酵素活性アッセイ.

主要な成果:

APOBEC3G触媒ドメインの溶液構造が決定され,5つのアルファヘリクスの配置が,5つのベータ鎖の水害性プラットフォーム上に示されました.
2つのアルファヘリクスが亜鉛調整活性部位を形成していることが確認された.
DNA結合モデルが提案され,陽性電荷の残留物が"縁"の位置に,触媒作用の標的であるサイトシンを配置することを示唆した.
構造とDNA結合モデルは,NMR,計算モデリング,系統遺伝データ,機能分析によってサポートされました.

結論:

APOBEC3G触媒ドメインの決定された構造は,DNAデアミナーゼと抗ウイルス活動のための分子基盤を提供します.
提案されたDNA結合モデルは,APOBEC3GがDNA基板とどのように認識し,相互作用するかについての洞察を提供します.
APOBEC3Gの構造を理解することで,関連する家族メンバーの機能やウイルスタンパク質との相互作用に関する研究が容易になり,抗ウイルス戦略の開発に潜在的に役立ちます.

さらに関連する動画

Determining 3'-Termini and Sequences of Nascent Single-Stranded Viral DNA Molecules during HIV-1 Reverse Transcription in Infected Cells

Determining 3'-Termini and Sequences of Nascent Single-Stranded Viral DNA Molecules during HIV-1 Reverse Transcription in Infected Cells

Published on: January 30, 2019

Probing The Structure And Dynamics Of Nucleosomes Using Atomic Force Microscopy Imaging

Probing The Structure And Dynamics Of Nucleosomes Using Atomic Force Microscopy Imaging

Published on: January 31, 2019

関連する概念動画

RNA Editing

RNA Editing

RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...

Leaky Scanning

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...

Exon Recombination

Exon Recombination

The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon...

Nucleic Acid Structure

Nucleic Acid Structure

The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA...

Viruses with RNA Genomes

Viruses with RNA Genomes

RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...

Inhibitors of Viral Protein Synthesis

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...