Structural studies of hGBP1 helical domain (alpha7-alpha13)

The INF-γ inducible guanylate binding proteins (GBP) belongs to the family of large GTP - binding proteins including Mx and dynamin. GBP1 plays an important role in the host defense against intracellular pathogens⁽¹⁾. The common property of hGBP´s is the ability to undergo oligomerization as a function of GTP binding and hydrolysis. Structurally the human GBP1 full length is composed of a LG (Large G) domain and an elongated α-helical domain⁽²⁾. Binding of GTP induces the formation of dimers interacting at the LG-domains, whereas in the presence of GDP.AlF*, this protein is able to form tetramers⁽³⁾. The interaction of the LG-Domains within this complex is well characterized by various biochemical experiments and the X-ray structure shows it as a dimer⁽⁴⁾.

The aim of this study is to elucidate the complex formation using the helical part of this protein as the second interaction domain. Therefore, we have determined the three-dimensional structure of hGBP1 helical domain (α7-α13) by solving the X-ray structure at 2.5Å resolution. We found out that the isolated helical domain (α7-α13) is able to form dimers in the crystal structure, as well. Furthermore, as the full length structure shows back folding of helix α13 our new data of the α7-α13 helical domain indicates structural changing by an elongation of helices α12 and α13α.