Biology Reference
In-Depth Information
Virus-receptor Complexes
A number of picornaviruses in complex with their respective recom-
binant soluble receptor fragments have been analyzed by cryo-
electron microscopy (cyro-EM).
36,52-56
These medium-resolution
structures, together with available X-ray structures of the viruses and
receptors, were used for building models of the complexes that have,
at present, attained a resolution of less than 10 Å.
57
Although, this
does not allow for the detailed interpretation of amino acid residue
contacts, it permits rather exact delineation of the interface. For
example, for the complexes between HRV14 or HRV16 and ICAM-1
the footprint area was determined to be about 1,400 Å
2
; the param-
eters of HRV14 and HRV16 binding to wt ICAM-1 and to an
ICAM-1 mutant were interpreted in the context of the contact
residues.
57
The first X-ray structure of a complex between the minor group
rhinovirus HRV2 and two modules of the very-low density lipopro-
tein receptor (V23) has been solved and revealed an intricate pattern
of ionic, electrostatic and hydrophobic interactions.
58
In this case, the
surface area of the receptor footprint is only 430 Å
2
, and is therefore
much inferior to that of the complexes between the major group
viruses and ICAM-1. This has important consequences for the bind-
ing mode of these receptors.
In the following section we will concentrate on the early events of
infection of representatives of the two receptor groups of human rhi-
noviruses, exemplified by the most extensively studied major group
virus HRV14 (and in some cases HRV3 and HRV16) and the minor
group virus HRV2. In Fig. 2 the different receptor binding sites on the
respective viruses are illustrated in a side view of VP1 of HRV2 and
HRV16. Whereas the tip of the amino terminal domain of ICAM-1 is
seen to enter the canyon of HRV16, the single V3 module of VLDLR
attaches sidewise to the protruding BC, DE, and HI loops of VP1 of
HRV2. The superposition also demonstrates the very similar folding
pattern of VP1 of the two viral serotypes. Figure 3 depicts the orienta-
tion of ICAM-1 versus V3 on a pentamer of the respective virus. Bound
receptors were tilted by 180
to the right to allow viewing of the con-
tact areas. Again, only the tip of the first domain of ICAM-1 is seen to
°
