3L88

Crystal structure of the human Adenovirus type 21 fiber knob

Summary for 3L88

• Entry DOI: 10.2210/pdb3l88/pdb
• Related: 2QLK 3BQ4 3EXV 3L89
• Descriptor: Fiber protein, SODIUM ION, GLYCEROL, ... (5 entities in total)
• Functional Keywords: adenovirus, fiber knob, viral protein
• Biological source: Human adenovirus 21
• Total number of polymer chains: 12
• Total formula weight: 267317.74

Authors

Cupelli, K.,Jost, M.,Persson, B.D.,Stehle, T. (deposition date: 2009-12-30, release date: 2010-04-14, Last modification date: 2023-09-06)

Primary citation

Cupelli, K.,Muller, S.,Persson, B.D.,Jost, M.,Arnberg, N.,Stehle, T.
Structure of adenovirus type 21 knob in complex with CD46 reveals key differences in receptor contacts among species B adenoviruses.
J.Virol., 84:3189-3200, 2010

PubMed Abstract: The complement regulation protein CD46 is the primary attachment receptor for most species B adenoviruses (Ads). However, significant variability exists in sequence and structure among species B Ads in the CD46-binding regions, correlating with differences in affinity. Here, we report a structure-function analysis of the interaction of the species B Ad21 knob with the two N-terminal repeats SCR1 and SCR2 of CD46, CD46-D2. We have determined the structures of the Ad21 knob in its unliganded form as well as in complex with CD46-D2, and we compare the interactions with those observed for the Ad11 knob-CD46-D2 complex. Surface plasmon resonance measurements demonstrate that the affinity of Ad21 knobs for CD46-D2 is 22-fold lower than that of the Ad11 knob. The superposition of the Ad21 and Ad11 knob structures in complex with CD46-D2 reveals a substantially different binding mode, providing an explanation for the weaker binding affinity of the Ad21 knob for its receptor. A critical difference in both complex structures is that a key interaction point, the DG loop, protrudes more in the Ad21 knob than in the Ad11 knob. Therefore, the protruding DG loop does not allow CD46-D2 to approach the core of the Ad21 knob as closely as in the Ad11 knob-CD46-D2 complex. In addition, the engagement of CD46-D2 induces a conformational change in the DG loop in the Ad21 knob but not in the Ad11 knob. Our results contribute to a more profound understanding of the CD46-binding mechanism of species B Ads and have relevance for the design of more efficient gene delivery vectors.

PubMed: 20071571
DOI: 10.1128/JVI.01964-09

Experimental method

X-RAY DIFFRACTION (2.5 Å)