C O N P S
On the previous two pages, the structure-function relationship and orthologs of melanoma inhibitory activity(MIA) are described. This page will illuminate the structure of MIA and hopefully clarify the structure-function relationship.
Through chime , various structures of a molecule can be highlighted and/or magnified. After manipulating the molecule on your own, go down the page to highlight important parts of MIA and get a better understanding of how form equals function in this protein.
Reset the view of melanoma inhibitory activity. Click here.
Illuminate the secondary structure of MIA. Click here. The beta sheets are yellow and alpha helices are pink. White signifies no secondary structure.
MIA contains an Src homology 3 (SH3) domain. Other proteins have been found to contain an SH3 domain, but MIA is the first secreted protein with this domain. The SH3 subdomain forms a beta barrel in MIA. View one end of barrel. Click here.
The SH3 domain in MIA is located between amino acids 21-89. To turn the SH3 domain in MIA orange, click here.
Characteristic of SH3 domains is an RT loop, which is formed between two beta sheets. This loop is important for determining ligand specificity. In other proteins that contain the SH3 domain a polyproline helix can bind to this loop. To make the loop appear purple click here.
The stabilization of the RT loop in MIA is different in other proteins. In other proteins the loop is stabilized by hydrogen bonds, while in MIA the loop is stabilized by a disulfide bridge and some hydrogen bonding. To illuminate the two cysteines (red) in MIA that form the disulfide bridge in, click here.
The ligand recognition site in MIA is undetermined, but a hydrophobic region created by 8 amino acids may be involved in ligand recognition. These amino acids are conserved in all SH3 domains and form the polyproline binding site in other proteins. Click here to highlight the eight amino acids and view the hydrophobic area.
The MIA protein does not bind to a polyproline helices ( a trait common to other proteins with the SH3 domain), because of a dissimilarity in the amino acids present at the normal binding site for a polyproline helix. The non-conserved residues in MIA, F59, I83, and Q28, change the shape of MIA, thus disabling the molecule's ability to bind to a polyproline helix. Click here to view the surface of MIA with F59 (purple), I83(blue), and Q28 (orange) highlighted. In order to view any of the other buttons after this one, the page needs to be reloaded. Click here to reload.
Lougheed, J.C ., J.H., T.A., F. B., T. H. Structure of melanoma inhibitory activity protein, a member of recently identified family of secreted proteins. Proceedings of the National Academy of Sciences of the United States of America 98:10 pgs. 5515-5520