Biology Reference
In-Depth Information
α2β1
integrin include, in addition to various collagen subtypes, other matrix
molecules such as laminin-1. 12 The
direct contacts with the natural ligands. 11 The natural ligands of
2I domain can recognize specific
triple helical motifs in collagens and bind to them with a relatively high
affinity. The best known motif is GFOGER (O
α
=
hydroxyproline). 13
integrin. 9 Blocking assays using
monoclonal antibodies against putative EV1 receptors have shown that
antibodies against
EV1 binds specifically to
α 2β 1
2 integrin subunits are the most potent blockers of
EV1 infection. 9 Despite the fact that antibodies against
α
2 microglob-
ulin have shown blocking effects, it is still unclear whether this mole-
cule plays any direct role in EV1 infection. 9 Integrin
β
α 2β 1
binds to EV1
using the
2I domain, and the binding site is close to the collagen-bind-
ing MIDAS. However, the two binding sites are clearly distinct and the
adhesion of
α
2I to EV1 is not dependent on Mg ++ . 14,15 Molecular mod-
eling, based on the cryo-EM structure of
α
α
2I-EV1 complex, showed
that
2I domain binds within the canyon (a depression surrounding
the 5-fold symmetry axis) on the EV1 surface with contacts to both the
inner and outer canyon walls. 16 Furthermore, the superposition of the
α
α
2I-collagen structure with the model of
α
2I-EV1 complex shows
that when
2I is bound to EV1, the virus canyon floor makes it impos-
sible for the collagens to bind.
EV1 may rely on the fact that on the plasma membrane some of the
α 2β 1
α
integrins are usually free of natural ligands and therefore able to
bind to the virus. However, in solid-phase binding assays the avidity of
α
2I domain to EV1 has been estimated to be at least 10-fold stronger
than to collagen I. 16 The higher affinity of integrins to EV1 than to
their natural ligand gives EV1 an opportunity to exploit this receptor
for cellular entry even in collagenous tissues. In fact, our recent obser-
vations suggest that in cells inside 3D collagen gels there are receptors
available to mediate viral infection (Marjomäki, unpublished).
The EV1 capsid is a symmetric structure that consists of 60 pro-
tomers, each containing one integrin binding site. The adjacent binding
sites are located nearest to each other in the protomers around the 5-fold
axis. Molecular modeling shows that multiple
α 2β1
integrin heterodimers,
which are much larger structures that
2I domains alone, can simultane-
ously occupy adjacent binding sites on the EV1 capsid. 16 Furthermore,
our observations with confocal microscopy have shown that treatment of
α
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