BCH 3125 on Protein Structure and Function (Grade A)

Summary:

This report discusses the crystal structure of a concentrative nucleoside transporter (CNT) from Vibrio cholera. The CNT is crucial in transporting nucleosides into cells for various cellular processes. The structure of the CNT reveals its trimeric organization and the arrangement of its alpha-helical subunits. The transport domain of the protein contains binding sites for Na+ ions and uridine. The binding of uridine involves hydrogen bonds with specific residues and water molecules. The Na+ binding site and uridine binding site are separate but positioned in close proximity. The report proposes an alternative access mechanism for uridine transport, suggesting that the transport domain undergoes a conformational change to facilitate the movement of uridine across the membrane. The structure also highlights hydrophobic interactions and packing interactions between the trimer subunits. Overall, the study provides insights into the molecular architecture and function of the concentrative nucleoside transporter from Vibrio cholera.

Excerpt:

BCH 3125 on Protein Structure and Function

Crystal Structure of a Concentrative Nucleoside Transported from Vibrio Cholera at 2.4 Å
PDB accession code: 3TIJ
Pubmed ID code: 22407322

1. Transport of nucleosides into the cell is crucial for signal termination and DNA/RNA synthesis. Concentrative nucleoside transporters (CNTs) accomplish this using an ion gradient to assist secondary active transport and play a role in the transport of nucleoside-derived drugs. A CNT from Vibrio cholera (vcCNT) with 39% sequence homology to a human CNT (hCNT3) and uses a Na+ gradient for transport has been crystallized in complex with Na+ and the uridine.

vcCNT is a homotrimer transmembrane protein with three identical subunits positioned in a triangle. Each subunit can bind and transport nucleosides. Each subunit is an alpha-helical protein containing mostly transmembrane alpha helices and a few that span the surface of the membrane (figure 1). The alpha helices are arranged in roughly two subdomains: the scaffold domain (red in Figure 1f)(helices TM1, TM2, IH1, EH, TM3, and TM6) that forms a ring around the central transport domain, which is formed of two groups of helices (IH2, HP1a/b, TM4a/b and TM5 in one, IH3, HP2a/b, TM7a/b, and TM8 in the other). These two groups have structural symmetry.