4xyy

4xyy is the Protein Data Bank accession code for a high‑resolution crystal structure of the human tetraspanin protein CD81. The structure was determined by X‑ray crystallography at a resolution of 2.05 Å and was deposited in 2018. The crystal belonged to the orthorhombic space group P212121 and contained a single monomer in the asymmetric unit. The protein, comprising 260 amino acids, adopts the characteristic four‑transmembrane helix core of the tetraspanin family, with a large extracellular loop (EC2) that is highly flexible in solution but adopts a defined β‑sandwich fold in the crystal.

The dataset was collected at the Advanced Photon Source synchrotron facility, and molecular replacement was performed using a homology model based on the CD63 crystal structure. Refinement statistics are within the typical range for membrane proteins, with an R‑work of 18.3 % and an R‑free of 21.9 %. The structure reveals a conserved hydrophobic patch within the transmembrane region that may serve as a binding site for cholesterol or other lipids. The extracellular loop contains a long glycosylated side chain that stabilizes dimer formation through hydrogen bonding.

Because CD81 is a critical co‑receptor for hepatitis C virus entry, the 4xyy structure has been used in computational docking studies to identify small‑molecule inhibitors that could block viral attachment. The crystal also serves as a template for sequence‑based modeling of other tetraspanins, and it is frequently cited in studies investigating the role of tetraspanin webs in cell adhesion and signal transduction.