3CNC

Crystal Structure of Ad16 fiber knob

3CNC の概要

• エントリーDOI: 10.2210/pdb3cnc/pdb
• 分子名称: Fiber protein (2 entities in total)
• 機能のキーワード: adenovirus fiber knob, viral protein
• 由来する生物種: Human adenovirus 16 (virus)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 144689.71

構造登録者

Pache, L.,Venkataraman, S.,Nemerow, G.R.,Reddy, V.S. (登録日: 2008-03-25, 公開日: 2008-06-17, 最終更新日: 2024-04-03)

主引用文献

Pache, L.,Venkataraman, S.,Reddy, V.S.,Nemerow, G.R.
Structural variations in species B adenovirus fibers impact CD46 association
J.Virol., 82:7923-7931, 2008

PubMed Abstract: A majority of species B adenoviruses (Ads) use CD46 as their primary receptor; however, the precise mechanisms involved in the binding of different Ad types to CD46 have not been resolved. Although previous studies indicate close similarities between two members of species B2 Ads in their usage of CD46, our current investigations revealed a surprisingly low CD46 binding affinity of the species B1 Ad16 fiber knob (equilibrium dissociation constant of 437 nM). We determined the crystal structure of the Ad16 fiber knob and constructed a model of this protein in complex with CD46. A comparison of this model to that of the CD46-Ad11 complex revealed structural differences in the FG and IJ loops that are part of the CD46 binding site. An analysis of a panel of recombinant fiber knobs with mutations targeting these regions in Ad16 and Ad11 uncovered a major contribution of the FG loop on CD46 binding. Two extra residues in the FG loop of the Ad16 fiber significantly reduce receptor interaction. Although avidity effects permit the use of CD46 on host cells by Ad16, virus binding occurs with lower efficiency than with B2 Ad types. The longer FG loop of the Ad16 fiber knob also is shared by other species B1 Ad fibers and, thus, may contribute to the low CD46 binding efficiencies observed for these Ad types. Our findings provide a better understanding of how different Ad types associate with CD46 and could aid in the selection of specific Ad fibers for more efficient Ad gene delivery vectors.

PubMed: 18524830
DOI: 10.1128/JVI.00754-08

実験手法

X-RAY DIFFRACTION (2.4 Å)