Role of a Critical Histidine Residue of Human EGF in Growth Signaling

  Epidermal growth factor (EGF) is a small protein hormone that plays a critical role in regulating cell growth and proliferation. Because it promotes healing, EGF is used clinically to treat severe burns, ulcers, and postsurgical wounds. Salil K. Niyogi and his colleagues in the Protein Engineering Program of ORNL's Life Sciences Division have utilized site-directed mutagenesis to identify the amino acid residues in human EGF that are important for receptor binding and activation.

  Considerations of species conservation and spatial location in the tertiary structure of EGF led to the examination of histidine-16 of human EGF. The results indicate that histidine-16 contributes to receptor binding and activation through hydrogen-bonding reactions. Replacement of histidine-16 with better hydrogen-bonders like glutamine and asparagine led to significantly (two- to four-fold) enhanced receptor binding and activation. These results suggest the possibility of generating analogues of EGF with superior wound-healing properties by protein engineering.

Contact: S. K. Niyogi
Telephone: 423-574-1195
E-mail: ni2@ornl.gov