Structure analysis and homology modeling of carcinoembryonic antigen
Carcinoembryonic antigen (CEA), a highly glycosylated cell surface protein
is a widely distributed tumour marker. Although it is expressed in high
proportions on a variety of human tumours, notably of the colon but also of
the breast and lung, studies also reveal the presence of CEA in normal tissues.
Thus the distribution and possibly the functional role of CEA is complex.
Monoclonal antibodies (Mabs) against CEA have been used successfully for
redioimmuno-localization of tumors. However, little progress has been made
towards mapping the exact locations of these Mabs to the surface of CEA.
A carefully constructed epitope map should help to probe the function(s) and
help in the search for Mabs with greater binding affinity to this important
tumour marker.
The mature CEA (CEAM5_HUMAN) consists of 668 amino acids. The extracellular
region (35-677) consists of seven domains, each having sequence similarity
with immunoglobulin (Ig) domains. The sequence relationship with
the immunoglobulins suggests that the complete extracellular region
can be modelled with some confidence from Ig folds with know 3D structures.
It is possible to prediction the 3D structure of each of the seven
domains based on knowledge-based
homology modelling. A possible packing model between each of the
seven domains can be proposed and candidate residues can be labelled
for site-directed mutagenesis.
Exercises:
-
Search Swiss-Prot with entry name:
CEAM5_HUMAN,
find out the sequence features of this molecule, use dotmatcher to draw a
dotplot to show the repeated domains of this molecule.
-
Search Swiss-Prot with Protein Name: carcinoembryonic antigen, and Gene Name:
CEACAM*, and Organism: Homo sapiens to find different CEA members.
- Retrieve the N-terminal domain of the above CEA members, make sequence
alignment and construct a phylogeny tree.
- Make multiple sequence alignment among the N-terminal domain of CEAM5_HUMAN
and the first domain of CD2
(1HNF)
and CD4
(3CD4)
as well as the variable domain of the light chain of immunoglobulin
(7FAB)
- Download the crystal structure of CEAM5
(2QSQ)
and IgG
(1REI)
from PDB,, use Swiss PDBViewer to compare the stricture features of these
two molecules
Data
Web resources:
- CEA Family
- A website of CEA gene family with protein domain structure of individual members.
- HPA
- CEACAM5 expression profiles at Human Protein Atlas
- AAAAA - AHo's Amazing
Atlas of Antibody Anatomy (Switzerland)
- AAIR
- Antibody Antigen Information Resource