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X-ray structure of a minor group human rhinovirus bound to a fragment of its cellular receptor protein


Although many viral receptors have been identified, the ways in which they interact with their cognate viruses are not understood at the molecular level. We have determined the X-ray structure of a complex between calcium-containing modules of the very low-density lipoprotein receptor and the minor group human rhinovirus HRV2. The receptor binds close to the icosahedral five-fold vertex, with only one module per virus protomer. The binding face of this module is defined by acidic calcium-chelating residues and, in particular, by an exposed tryptophan that is highly conserved. The attachment site on the virus involves only residues from VP1, particularly a lysine strictly conserved in all minor group HRVs. The disposition of the attached ligand-binding repeats around the five-fold axis, together with the proximity of the N- and C-terminal ends of adjacent modules, suggests that more than one repeat in a single receptor molecule might attach simultaneously.

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Figure 1: Scheme of the modular organization of members of the LDLR family.
Figure 2: Three-dimensional structure of the V23–HRV2 complex.
Figure 3: Interactions between the V3 module from VLDLR and HRV2.
Figure 4: A concatamer with five copies of V3 protects HeLa cells against infection by all minor group HRVs.

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This work was supported by grants BIO2002-00517 and BIO2002-04419 of Comision Interministerial de Ciencia y Tecnología to N.V and I.F, respectively, and by the Austrian Science Foundation, grant number P-14503, to D.B. Data were collected at the European Molecular Biology Laboratory protein crystallography beamlines ID14.4 and ID29 at European Synchrotron Radiation Facility (ESRF, Grenoble) within a Block Allocation Group (BAG Barcelona). Financial support was provided by the ESRF and by grant HPRI-CT-1999-00022 of the European Union. We thank I. Goesler for expert technical assistance, E. Hewat for sending us the electron microscopy maps before publication and M.G. Rossmann, T. Skern and P.C. Loewen for critically reading the manuscript.

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Correspondence to Nuria Verdaguer.

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Verdaguer, N., Fita, I., Reithmayer, M. et al. X-ray structure of a minor group human rhinovirus bound to a fragment of its cellular receptor protein. Nat Struct Mol Biol 11, 429–434 (2004).

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