人間のXPAのDNA結合領域を再定義する
Norie Sugitani1, Steven M Shell, Sarah E Soss
1Departments of Biochemistry and Chemistry, and Center for Structural Biology, Vanderbilt University , Nashville, Tennessee 37232-8725, United States.
Journal of the American Chemical Society
|July 25, 2014
まとめ
Xeroderma pigmentosum補完群A (XPA) のDNA結合ドメイン (DBD) が再定義されました. 新しいXPA ((98-239) 構造は,全長タンパク質の親和性を持つDNAを結合し,DNA修復研究を支援する.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
- バイオケミストリー バイオケミストリー
背景:
- Xeroderma pigmentosum補完群A (XPA) タンパク質は,核酸切除修復 (NER) によるDNA修復に不可欠です.
- XPAは,NERタンパク質とDNAと相互作用して,支架として作用します.
- XPAのDNA結合ドメイン (DBD) の変異は,重度のXeroderma pigmentosum現象型と関連しています.
研究 の 目的:
- XPA DBDのDNA結合特性について説明します.
- XPA-DNA相互作用の分子基盤を調査する.
- DNA結合の研究に適したXPA構造を特定する.
主な方法:
- 光アニソトロピーDNA結合アッセイ.
- XPAのシーケンス分析.
- C端末のXPAコンストラクションの生成と分析 (XPA ((98-239)).
- 2次元の (15) N-(1) H NMRスペクトロスコーピー. 2次元の (15) N-(1) H NMRスペクトロスコーピー. 2次元の (15) N-(1) H NMRスペクトロスコーピー. 2次元の (15) N-(1) H NMRスペクトロスコーピー.
主要な成果:
- 以前定義されたXPA DBD (XPA(98-219)) は,DNA結合の afinity が弱いことを示している.
- 再定義されたXPAコンストラクート,XPA{98}-239は,全長XPAに匹敵するDNA結合親和性を示しています.
- XPA ((98-239) は,Y型のssDNA-dsDNA結合点と他のDNA基板に結合する.
- NMRデータは,XPA ((98-239) がDNA結合時に形状の変化を経験することを示唆しています.
結論:
- XPA DBDは,C端末残留を含めるように再定義されるべきである.
- XPA ((98-239) は,XPAのDNA結合活動を研究するためのより正確なモデルです.
- この発見は,DNA修復メカニズムとXeroderma pigmentosumの理解を進めています.
関連する概念動画
Conserved Binding Sites
4.1K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.1K
Conservation of Protein Domains Over Different Proteins
11.7K
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
11.7K
Inheritance of Chromatin Structures
6.0K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.0K
Single-Strand DNA Binding Proteins
12.8K
For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
12.8K
Gene Families
8.0K
Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes are mistakenly duplicated during cell division. Unlike their parent genes (which are subject to selection pressure to maintain function), these gene copies do not need to preserve their sequences and may evolve at a relatively faster rate.
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
8.0K
Euchromatin
6.7K
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
6.7K


