Abstract
Aminoacyl-tRNA synthetases-interacting multifunctional protein3 (AIMP3/p18) is involved in the macromolecular tRNA synthetase complex via its interaction with several aminoacyl-tRNA synthetases. Recent reports reveal a novel function of AIMP3 as a tumor suppressor by accelerating cellular senescence and causing defects in nuclear morphology. AIMP3 specifically mediates degradation of mature Lamin A (LmnA), a major component of the nuclear envelope matrix; however, the mechanism of how AIMP3 interacts with LmnA is unclear. Here we report solution-phase hydrogen/deuterium exchange (HDX) for AIMP3, LmnA, and AIMP3 in association with the LmnA C-terminus. Reversed-phase LC coupled with LTQ 14.5 T Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) results in high mass accuracy and resolving power for comparing the D-uptake profiles for AIMP3, LmnA, and their complex. The results show that the AIMP3-LmnA interaction involves one of the two putative binding sites and an adjacent novel interface on AIMP3. LmnA binds AIMP3 via its extreme C-terminus. Together these findings provide a structural insight for understanding the interaction between AIMP3 and LmnA in AIMP3 degradation.
Highlights
To investigate the role that AIMP3 plays in Lamin A (LmnA) degradation, we report solution-phase hydrogen/deuterium exchange (HDX) monitored by high resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) for AIMP3 and AIMP3 in complex with the LmnA C-terminus
Mapping the contact surfaces in the Lamin A:AIMP3 complex by H/D exchange FT-ICR mass spectrometry regions showing significant decreases in D-uptake, suggesting that AIMP3 binds LmnA through the interacting surface consisting of both putative (Interface I) and novel binding sites
HDX results for LmnA reveal that the C-terminal 7 residues are critical for its binding to AIMP3
Summary
Mapping the contact surfaces in the Lamin A:AIMP3 complex by H/D exchange FT-ICR mass spectrometry regions showing significant decreases in D-uptake, suggesting that AIMP3 binds LmnA through the interacting surface consisting of both putative (Interface I) and novel binding sites. HDX results for LmnA reveal that the C-terminal 7 residues are critical for its binding to AIMP3.
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