Integrative Structure of the SMC-5/6 -- NSE-2,5,6 Pentameric Complex.

Developed an integrative structure model of the (yeast) SMC5/6 proteins in complex with the SUMO ligase NSE2 and the associated NSE5/6 proteins. Structural Maintenance of Chromosomes (SMC) proteins are important chromatin modulators involved in DNA repair and regulation. Despite topological similarities with condensin and cohesin, the molecular bases of SMC5/6 remain poorly understood.

We combined crystal structures of the globular head and hinge regions, cryo-EM structure of the NSE5/6 sub-complex, in-silico designed coiled-coil structures of SMC5/6 arms, and 337 unique inter-residue chemical crosslinks to compute the integrative structure. The model is validated by negative-stain 2D class averages and high crosslink satisfaction. A key insight: SMC5/6 arms remain relatively straight, consistent with the crosslinking dataset.

• Published in PNAS, in collaboration with the Zhao, Patel, and Kentsis labs at Memorial Sloan Kettering Cancer Center.
• Deposited in PDB-Dev
• Modeling scripts