<h3>Title</h3>
<h3><span style="font-size: 12.16px;">A conserved and buried edge-to-face aromatic interaction in SUMO: Implications for SUMO pathway and viral replication</span></h3>
<p><strong><span style="text-decoration: underline;">Abstract</span> :</strong></p>
<p style="text-align: justify;"><span style="font-size: 12.16px;">Often multiple aromatic amino acids buried at a protein’s core are involved in mutual paired interactions. Although ab initio energy calculations have highlighted the importance of orientations between aromatic rings for stable aromatic interaction, studies in the context of a protein’s fold and function are elusive. Small Ubiquitin-Like Modifier (SUMO) is a common post-translational modifier that affects diverse cellular processes. Here, we report that a highly conserved aromatic triad is a unique signature of SUMO that is absent in other Ubiquitin Like homologous folds. The specific edge-to-face conformation between a pair of interacting aromatics in the triad is vital to the fold and stability of SUMO. NMR structural studies showed perturbation of the conformation of the aromatics disrupts several long-range tertiary contacts in SUMO, leading to a heterogeneous and dynamic protein with attenuated SUMOylation in both in-vitro and in cellular conditions. Our results highlight that absolute co-conservation of specific aromatic pairs inside a protein core is indispensable for its stability and function. The Human CytoMegaloVirus (HCMV) is a member of the gamma herpes virus family, whose life-cycle is significantly dependent on the host SUMOylation machinery.  IE2 is an immediate early expressed HCMV proteins, which regulate the viral replicative cycle. I will present results that uncover an unprecedented mechanism used by the viral transactivator IE2 to exploit a cross-talk of two post-translational modifications Phosphorylation and SUMOylation, to ensure an effective viral replication.</span></p>