Solution structure of the PWWP domain of the hepatoma‐derived growth factor family

Abstract

Among the many PWWP‐containing proteins, the largest group of homologous proteins is related to hepatoma‐derived growth factor (HDGF). Within a well‐conserved region at the extreme N‐terminus, HDGF and five HDGF‐related proteins (HRPs) always have a PWWP domain, which is a module found in many chromatin‐associated proteins. In this study, we determined the solution structure of the PWWP domain of HDGF‐related protein‐3 (HRP‐3) by NMR spectroscopy. The structure consists of a five‐stranded β‐barrel with a PWWP‐specific long loop connecting β2 and β3 (PR‐loop), followed by a helical region including two α‐helices. Its structure was found to have a characteristic solvent‐exposed hydrophobic cavity, which is composed of an abundance of aromatic residues in the β1/β2 loop (β‐β arch) and the β3/β4 loop. A similar ligand binding cavity occurs at the corresponding position in the Tudor, chromo, and MBT domains, which have structural and probable evolutionary relationships with PWWP domains. These findings suggest that the PWWP domains of the HDGF family bind to some component of chromatin via the cavity.