Crystal structures of PCNA1 and PCNA2 from Aeropyrum pernix: implications for a distorted heterotrimeric sliding clamp.

Aeropyrum pernix is a hyperthermophilic archaeon that possesses three proliferating cell nuclear antigen (PCNA) isoforms (ApePCNA1, ApePCNA2 and ApePCNA3) that form a heterotrimeric sliding clamp. To gain more detailed structural insights into this heterotrimeric assembly, we determined the crystal structures of ApePCNA1 and ApePCNA2. ApePCNA1 was crystallized under a new condition, and the 1.60 Å resolution structure revealed a unique nonproline cis-peptide bond between Arg187 and Arg188, which was not deeply discussed in a previous report. The structure of ApePCNA2 was determined at 2.17 Å resolution, and it forms a typical homotrimeric ring. In the cubic crystal form, its crystal packing shows an intriguing tetrahedral assembly of four trimers. Modeling the ApePCNA1-ApePCNA2-ApePCNA3 heterotrimer based on these structures suggests that the cis-peptide in ApePCNA1 induces significant steric hindrance at the subunit interface, leading to a symmetry-broken or distorted ring conformation rather than the canonical pseudo-threefold-symmetric assembly.