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Function of your Protein

, specifically Epa9, it binds to a host cell (human epithelial cell) to provide a host cell recognition to invade the host. In this case, this epithelial adhesion belongs to the fungus Candida glabrata. This fungus has more than just one Epa to create host cell recognition, it has over 20 Epa's. These proteins can adhere Candida glabrata to a human epithelial cell by specifically binding to different carbohydrates on the outside of the cell. This interaction between the Epas and the carbohydrates is what creates the adhesion for host cell recognition.

Biological relevance and broader implications

Candida glabrata is a fungus of high concern as it infects the host through the bloodstream. Unfortunately, this is a life-threatening infection for humans and upwards of 29% of all cases are life-threatening. As this does affect the human race is it of high relevance to study in health sciences. Understanding how this fungus can infect the bloodstream is needed to slow and possibly stop Candida glabrata from infecting other people. The approach in this paper is on the epithelial adhesions and altering their composition around the binding site. By altering conserved and un-conserved areas in its binding site we can better understand what hot spots are needed for good binding to the carbohydrates on the human epithelial cells. Understanding this protein's function is beneficial to understanding how other possible fungi infect hosts in a parasitic relationship. In this page we will highlight Epa9 specifically and how it can bind compared to other mutants created from the paper.

Important amino acids

Structural highlights

Some things to note are that the main structure of the protein consists of . The rest of the molecule contains a primary chain structure. It can also be noted that two beta-sheets contain at least one key residue that interacts with the ligand. These parts of the beta-sheets help to form the pocket to bind the ligand best suited for the structure. The rest of the binding site has some that help shape the pocket for binding the ligand as well. This includes two outer loops (Loop 1 and loop 2), two calcium-binding loops (CBL1 and CBL2). The outer two loops are highly variable as compared to the highly conserved inner CBL1. The loop is conservative as it is crucial for having good host cell binding. The other calcium-binding loop (2) is variable and tied to the protein's ligand-binding specificity. The outer pocket is made of three other loops these are more variable, but still contain some key residues that are correlated with high binding affinity. To get a better look at the shape of the pocket here is a . We can observe that the shape of the binding pocket is dipped in and we can see where the outer two loops help shape that pocket as well as the inner CBL1 and CBL2. This allows for the space to interact with the carbohydrates on the host cell surface. Though it is hard to see with this view we can also understand how the variable loops can allow for conformational change for different carbohydrates to fit into the pocket and interact by hydrogen bonding to key residues.

Other important features

To look further into the structure studied we are going to compare two of the versions of the Epa's from the paper cited below. First looking at Epa9, this structure off to the right we can see the elongated loop 1. It was highlighted that this loop is important to the structure as it binds bigger sugars than an Epa1. It stays in an open state when bound to a bigger sugar, but as shown here it is in a more closed state as it is bound to a smaller sugar. Now looking at another structure for comparison, a mixed version of Epa9, but the only difference is that its CBL2 loop is from Epa1.