Comparative Analysis of EGFR

Conducting comparative analysis of known protein structures to unknown protein structures of allows researchers and scientists to develop theories about protein behavior. Here we investigate the structural differences of inactive EGFR and a mutant EGFR in order to understand the how pharmaceutical products prevent cellular proliferation.

Protein Description

EGFR is an important protein for a variety of different types of oncology. It is important for development of mammary glands. It’s ligands ( TGF-α, and heregulin) play such vital roles in development, that in the absence of hormone signals can still induce ductal and lobuloaveolar development.

Protein Location

EGFR is located on the surface of cells throughout the body. When activated by different cytokines, receptors dimerize and initiates downstream signaling via its intracellular tyrosine kinase domains.

EGFR Media Gallery

Protein Structure

Dimerization stimulates the intracellular tyrosine kinase domains. This begins a process where several tyrosine residues are autophosphorylated. (Y992, Y1068, Y1148, Y1173 ). Downstream signaling following this include MAPK, Akt, and HNK pathways. These lead to both DNA synthesis and cellular proliferation. If this process becomes uncontrolled, unfortunate diseases states develop.

Inactive EGFR 3D Animation

3-Dimensional States

Tryosine Kinases exist in two distinct states, inactive and active. Inactive states are marked by their contracted a-loop with a closed N-lobe. When closed, the ATP binding pocket of the tyrosine kinase is blocked. and tyrosine residues are protected from phosphorylation. In the active state, the a-loop is extended with an open N-lobe revealing the ATP-binding pocket of the kinase.

Role in Health and Disease


Mutations that lead to over expression of EGFR or within in different residues of EGFR tyrosine kinase, lead to different types of cancers as cells continually over express and proliferate.

Mutant Active EGFR 3D Animation

Inflammatory Disease

Cancer isn’t the only issue. Psoriasis, eczema, and atherosclerosis are all implicated in over-expression of EGFR. This is not well understood yet, but likely due to over-expression of inflammatory cytokines that initiate EGFR phosphorylation.

Drug Therapies

A common strategy of small molecule inhibitors is to identify receptors and examine their intra-cellular kinase domains. In many cases, this prevents aberant behaviors in the receptor and mitigate the develop of disease. An easy target for this inhibition process is the kinase domain’s ATP binding pocket. It has a high affinity for its ligand, and phosphorylation of its tyrosine residue a requirement for signal propogation.

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