A cellular receptor of human rhinovirus type 2, the very-low-density lipoprotein receptor, binds to two neighboring proteins of the viral capsid.
The very-low-density lipoprotein receptor (VLDL-R) is a receptor for the minor-group human rhinoviruses (HRVs). Only two of the eight binding repeats of the VLDL-R bind to HRV2, and their footprints describe an annulus on the dome at each fivefold axis. By studying the complex formed between a selection of soluble fragments of the VLDL-R and HRV2, we demonstrate that it is the second and third repeats that bind. We also show that artificial concatemers of the same repeat can bind to HRV2 with the same footprint as that for the native receptor. In a 16-A-resolution cryoelectron microscopy map of HRV2 in complex with the VLDL-R, the individual repeats are defined. The third repeat is strongly bound to charged and polar residues of the HI and BC loops of viral protein 1 (VP1), while the second repeat is more weakly bound to the neighboring VP1. The footprint of the strongly bound third repeat extends down the north side of the canyon. Since the receptor molecule can bind to two adjacent copies of VP1, we suggest that the bound receptor "staples" the VP1s together and must be detached before release of the RNA can occur. When the receptor is bound to neighboring sites on HRV2, steric hindrance prevents binding of the second repeat.
Neumann
Emmanuelle
E
Institut de Biologie Structurale Jean-Pierre Ebel, 38027 Grenoble, France.
Moser
Rosita
R
Snyers
Luc
L
Blaas
Dieter
D
Hewat
Elizabeth A
EA
D001665:Binding Sites; D002213:Capsid / Q000737:chemistry*; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D006801:Humans; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D011973:Receptors, LDL / Q000737:chemistry / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D012229:Rhinovirus / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*
D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D011991:Receptors, Virus; C036053:VLDL receptor; D014764:Viral Proteins; C074995:viral protein 1, rhinovirus