Biology Reference
In-Depth Information
the cytosol, where it initiates the replication cycle. The molecular mechanisms
of viral uncoating and release of RNA from caveosomes still remain unknown.
α 2β 1
Integrin
is the Cellular Receptor for
Echovirus 1
The integrins are a large family of cell adhesion receptors. They are
heterodimers formed by an
α
and a
β
subunit (for review see Ref. 1).
V subunit are internalization receptors
for a large number of viruses, including adenoviruses, coxsackie viruses,
foot-and-mouth-disease viruses and parechovirus 1.
2-6
The integrins that contain the
α
V integrins bind
to a short RGD (arginine-glysine-aspartic acid) motif in both natural
ligands and viruses, and they can guide the ligands into clathrin-
coated vesicles and early endosomes.
2,7
α
In addition to
α
V integrins,
belongs
to the subgroup of collagen binding integrins (for review see Ref. 8).
Echovirus 1 (EV1) binds to this integrin
9
and the virus-integrin com-
plex is internalized via a different entry pathway when compared to
α
other integrins may also act as virus receptors. Integrin
α2β1
V integrin-dependent viruses.
10
EV1 is a non-enveloped human pathogen belonging to the
Enterovirus genus of the
Picornaviridae
family. In humans, echovirus
infections are associated with meningitis, encephalitis, respiratory
infections and diarrhea. EV1, like all picornavirus particles, is com-
posed of a single RNA molecule of positive polarity and an icosahe-
dral capsid consisting of VP1-4 proteins forming 60 protomers that
surround the RNA. We have studied the molecular mechanisms of
α2β1
integrin-EV1 interactions to shed light on the role of receptor
action in the process of virus entry.
α
α
β
1 Integrin
and Induces Clustering of the Receptor Molecules
EV1 Binds to
2I Domain in the
2
The integrins that act as collagen receptors contain a special inserted
domain (
α
I domain) in their
α
subunit, which binds their natural lig-
ands. The
I domain has a typical Rossman fold and a metal ion
coordination site (MIDAS), containing an Mg
++
ion. In
α
I domain
the metal ion and certain neighboring amino acid residues form
α2
