Biology Reference
In-Depth Information
identified is a CEACAM1 (carcinoembryonic antigen cell adhesion mol-
ecule 1) that serves as an MHV receptor. CEACAM1 is classified in the
immunoglobulin (Ig) superfamily.
25,26
The prototype CEACAM1 is
composed of four Ig-like ectodomains (in the order of N, A1, B and A2
from the N terminus), a transmembrane domain, and a cytoplasmic tail
(Cy). There are four isoforms, two of which have 4 Ig-like domains, and
the other two, two Ig-like domains (N and A2), one of which has either
a long or short Cy.
27
Allelic forms are known for CEACAM1, CEA-
CAM1
a
and CEACAM1
b
, the former being expressed in most labora-
tory mouse strains susceptible to MHV and the latter in SJL relatively
resistant to MHV.
27,28
CEACAM1 is expressed on various epithelial cells,
endothelial cells and hemopoietic cells.
29
It functions as a cell adhesion
molecule,
30
a signaling molecule and an angiogenic factor.
31
The virus-binding site of CEACAM1 is located in the N
domain.
32,33
Crystal structural analysis of CEACAM1 revealed that a
uniquely folded CC´-loop that protrudes from the N domain mass
plays an important role in virus binding.
34
This region also partici-
pates in homophilic adhesion activity that is retained by CEACAM1.
34
The receptor for SARS-CoV was identified as an angiotensin-con-
verting enzyme 2 (ACE2).
35
ACE2 is a type I integral membrane pro-
tein with carboxypeptidase activity and plays an important role in the
rennin angiotensin system for blood pressure homeostasis. ACE2 is
expressed in a variety of organs, such as the lungs and intestines, the
main target organs of SARS-CoV, as well as in the heart or kidneys
where SARS-CoV infection is rarely observed or limited.
36
As for the
virus binding site on ACE2, it was postulated from the homology to
other proteins (whose crystal structure was studied), that a negatively
charged ridge close to the deep channel containing a catalytic site is
the virus-binding site.
37
Recently, the more precise binding site was
determined to locate to
α
-helix 1 of ACE2 and to a loop leading to
-sheets.
38
The other coronavirus receptor is aminopeptidase N (APN) that
serves as a receptor for group I coronaviruses.
39
Being similar to
ACE2, APN is a zinc metalloprotease. Group 1 coronaviruses infect-
ing different species of animals utilize APN of the host species,
though feline APN serves as a receptor for porcine, human and canine
coronaviruses as well.
39
β
