3L89

Human Adenovirus type 21 knob in complex with domains SCR1 and SCR2 of CD46 (membrane cofactor protein, MCP)

Summary for 3L89

• Entry DOI: 10.2210/pdb3l89/pdb
• Related: 1CKL 2O39 3L88
• Descriptor: Fiber protein, Membrane cofactor protein, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: adenovirus, fiber knob, viral protein, membrane cofactor protein, mcp, virus receptor complex, scr, short consensus repeat, ccp, complement control protein, complement pathway, glycoprotein, host-virus interaction, immune response, innate immunity, sushi2, viral protein-protein binding complex, viral protein/protein binding
• Biological source: Human adenovirus 21; More
• Total number of polymer chains: 24
• Total formula weight: 441721.01

Authors

Cupelli, K.,Stehle, T. (deposition date: 2009-12-30, release date: 2010-04-14, Last modification date: 2024-10-09)

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 (3.5 Å)