Chlamydia protein Pgp3 studied at high resolution in a new crystal form

Abstract

The protein Pgp3 is implicated in the sexually transmitted disease chlamydia and comprises an extended complex arrangement of a C terminal domain (CTD) and an N terminal domain (NTD), each linked by a triple helix coiled coil (THCC). We report the X-ray crystal structure of Pgp3 from a LGV1 strain at the highest X-ray diffraction resolution obtained to date for the full protein. The protein was crystallised using a high KBr salt concentration, which resulted in a new crystal form with relatively low solvent content diffracting to a resolution of 1.98 Å. We describe the 3D structure of this new crystal form, compare it with other crystal forms, describe the KBr salt binding sites and the relevance to chlamydia isolates from around the globe. The crystal packing is apparently driven by the CTDs. Since the three fold axes of the THCC and NTD are not collinear with a CTD’s three fold axis this naturally leads to a disorder in the THCC and the portion of the NTD not directly interacting with the CTD via crystal packing. The key avenue to resolve these oddities of the crystal structure analysis was a complete new analysis in space group P1 and determining the space group as P212121. This space group assignment was the one originally determined from the diffraction pattern but perhaps complicated by a translational non crystallographic symmetry. We found this crystal structure of a three domain multi macromolecular complex, with two misaligned three fold axes, a unique challenge, something not encountered before. A specific intermolecular interaction, possibly of functional significance in receptor binding in chlamydia, we suggest might allow design of a new chemotherapeutic agent against chlamydia.