3cnc
From Proteopedia
Crystal Structure of Ad16 fiber knob
Overview
A majority of species B adenoviruses uses 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 adenoviruses in their usage of CD46, our current investigations revealed a surprisingly low CD46 binding affinity of the species B1 Ad16 fiber knob (KD of 437 nM). We determined the crystal structure of Ad16 fiber knob and constructed a model of this protein in complex with CD46. 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. 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 Ad16 use of CD46 on host cells, virus binding occurs with lower efficiency than with B2 Ad types. The longer FG loop of the Ad16 fiber knob is also 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 the selection of specific Ad fibers for more efficient adenoviral gene delivery vectors.
About this Structure
3CNC is a Single protein structure of sequence from Human adenovirus 16. Full crystallographic information is available from OCA.
Reference
Structural Variations in Species B Adenovirus Fibers Impact CD46 Association., Pache L, Venkataraman S, Reddy VS, Nemerow GR, J Virol. 2008 Jun 4;. PMID:18524830 Page seeded by OCA on Wed Jun 18 12:11:01 2008
