6J4I

A conserved and buried edge-to-face aromatic interaction in SUMO is vital for the SUMO pathway

Summary for 6J4I

• Entry DOI: 10.2210/pdb6j4i/pdb
• Descriptor: Small ubiquitin-related modifier 1 (1 entity in total)
• Functional Keywords: post-translational modifier, immune system
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 12389.86

Authors

Chatterjee, K.S.,Das, R. (deposition date: 2019-01-09, release date: 2019-03-13, Last modification date: 2024-05-15)

Primary citation

Chatterjee, K.S.,Tripathi, V.,Das, R.
A conserved and buried edge-to-face aromatic interaction in small ubiquitin-like modifier (SUMO) has a role in SUMO stability and function.
J.Biol.Chem., 294:6772-6784, 2019

PubMed Abstract: Aromatic amino acids buried at a protein's core are often involved in mutual paired interactions. energy calculations have highlighted that the conformational orientations and the effects of substitutions are important for stable aromatic interactions among aromatic rings, but 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 of three amino acids, Phe-Tyr-Phe, is a unique SUMO signature that is absent in other ubiquitin-like homologous folds. We found that a specific edge-to-face conformation between the Tyr-Phe pair of interacting aromatics is vital to the fold and stability of SUMO. Moreover, the noncovalent binding of SUMO-interacting motif (SIM) at the SUMO surface was critically dependent on the paired aromatic interactions buried at the core. NMR structural studies revealed that perturbation of the Tyr-Phe conformation disrupts several long-range tertiary contacts in SUMO, leading to a heterogeneous and dynamic protein with attenuated SUMOylation both and in cells. A subtle perturbation of the edge-to-face conformation by a Tyr to Phe substitution significantly decreased stability, SUMO/SIM affinity, and the rate of SUMOylation. Our results highlight that absolute co-conservation of specific aromatic pairs inside the SUMO protein core has a role in its stability and function.

PubMed: 30824543
DOI: 10.1074/jbc.RA118.006642

Experimental method

SOLUTION NMR