Modulation of the Vault Protein-Protein Interaction for Tuning of Molecular Release

• DOI: 10.1038/s41598-017-12870-x
• Publication Date: 2017-10-26T11:32:26Z
• Authors: Kang Yu; Yin Hoe Yau; Ameya Sinha; Tabitha Tan; Valerie A. Kickho...; Leonard H. Rome; Hwankyu Lee; Susana G. Shochat; Sierin Lim
• Keywords: Vault (architecture); Modulation (music)

Abstract Vaults are naturally occurring ovoid nanoparticles constructed from a protein shell that is composed of multiple copies major vault (MVP). The vault-interacting domain poly(ADP-ribose)-polymerase (INT) has been used as shuttle to pack biomolecular cargo in the lumen. However, interaction between INT and MVP poorly understood. It hypothesized release rate lumen related INT. To tune molecular cargos nanoparticles, we determined interactions isolated INT-interacting domains (iMVP) wild-type compared them two structurally modified INT: 15-amino acid deletion at C terminus (INTΔC15) histidine substituted surface (INT/DSA/3 H) impart pH-sensitive response. apparent affinity constants using plasmon resonance (SPR) biosensor technology 262 ± 4 nM for iMVP/INT, 1800 160 iMVP/INTΔC15 pH 7.4. INT/DSA/3 H exhibits stronger iMVP ( K D app = 24 nM) dissociates slower than 6.0.