No abstract

Ankylosing Spondylitis is an autoimmune disease leading to inflammation in the joints and ligaments of the spine. ERAP1 is a major risk factor for AS and ERAP1 mutations may result in structural changes that alter the trimming efficiency, thereby altering the immune response. The underlying structural mechanisms of AS pathogenesis have not yet been fully elucidated. This study investigated ERAP1/ERAP2 allotypes using Molecular Dynamics in both monomeric and dimeric forms. ERAP1's domain IV has been found to be a favorable region for dimerization. Different allotype dimers exhibited different stability characteristics. Furthermore, the effects of allotypic variation were more pronounced in Hap2-/Hap8-coupled dimer structures and were more distinct in heterodimers. An analysis of the interchain region revealed that both H-bonding and electrostatic interactions between chains of Hap2–N392 heterodimer structures were lower than those between Hap2–Hap2 revealing that allotypic variations played a significant role in stabilizing and destabilizing dimer structures.