Applied Bioinformatics Course [中文]

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.



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6 July 2024, J Luo, CBI, PKU, Beijing, China