4AR2

Dodecahedron formed of penton base protein from adenovirus Ad3

4AR2 の概要

• エントリーDOI: 10.2210/pdb4ar2/pdb
• 関連するPDBエントリー: 1QHV 1QIU 1V1H 1V1I 2C9F 4AQQ
• 分子名称: L2 PROTEIN III (PENTON BASE), FIBER PROTEIN, CALCIUM ION (3 entities in total)
• 機能のキーワード: viral protein, capsid protein, dsdna virus, dodecahedron, virus-like particle, strand swapping
• 由来する生物種: HUMAN ADENOVIRUS 3; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 60613.20

構造登録者

Burmeister, W.P.,Szolajska, E.,Zochowska, M.,Nerlo, B.,Andreev, I.,Schoehn, G.,Andrieu, J.-P.,Fender, P.,Naskalska, A.,Zubieta, C.,Cusack, S.,Chroboczek, J. (登録日: 2012-04-20, 公開日: 2012-10-24, 最終更新日: 2023-12-20)

主引用文献

Szolajska, E.,Burmeister, W.P.,Zochowska, M.,Nerlo, B.,Andreev, I.,Schoehn, G.,Andrieu, J.P.,Fender, P.,Naskalska, A.,Zubieta, C.,Cusack, S.,Chroboczek, J.
The Structural Basis for the Integrity of Adenovirus Ad3 Dodecahedron.
Plos One, 7:46075-, 2012

PubMed Abstract: During the viral life cycle adenoviruses produce excess capsid proteins. Human adenovirus serotype 3 (Ad3) synthesizes predominantly an excess of free pentons, the complexes of pentameric penton base and trimeric fiber proteins, which are responsible for virus penetration. In infected cells Ad3 pentons spontaneously assemble into dodecahedral virus-like nano-particles containing twelve pentons. They also form in insect cells during expression in the baculovirus system. Similarly, in the absence of fiber protein dodecahedric particles built of 12 penton base pentamers can be produced. Both kinds of dodecahedra show remarkable efficiency of intracellular penetration and can be engineered to deliver several millions of foreign cargo molecules to a single target cell. For this reason, they are of great interest as a delivery vector. In order to successfully manipulate this potential vector for drug and/or gene delivery, an understanding of the molecular basis of vector assembly and integrity is critical. Crystallographic data in conjunction with site-directed mutagenesis and biochemical analysis provide a model for the molecular determinants of dodecamer particle assembly and the requirements for stability. The 3.8 Å crystal structure of Ad3 penton base dodecamer (Dd) shows that the dodecahedric structure is stabilized by strand-swapping between neighboring penton base molecules. Such N-terminal strand-swapping does not occur for Dd of Ad2, a serotype which does not form Dd under physiological conditions. This unique stabilization of the Ad3 dodecamer is controlled by residues 59-61 located at the site of strand switching, the residues involved in putative salt bridges between pentamers and by the disordered N-terminus (residues 1-47), as confirmed by site directed mutagenesis and biochemical analysis of mutant and wild type protein. We also provide evidence that the distal N-terminal residues are externally exposed and available for attaching cargo.

PubMed: 23049939
DOI: 10.1371/JOURNAL.PONE.0046075

実験手法

X-RAY DIFFRACTION (3.8 Å)