Aminoacyl-tRNA synthetases-interacting multifunctional protein3 (AIMP3/p18) is involved in the macromolecular tRNA synthetase complex via its interaction with several aminoacyltRNA 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.
Bibliographical noteFunding Information:
This research was supported by National Science Foundation Division of Materials Research through DMR-06-54118 (AM) (URL: (https://www.nsf.gov/div/index.jsp?div=DMR)), the Global Frontiers Project [NRFM1AXA002-2011-0028417] (URL: http://www.globalfrontiersproject.org/) and the WCU project [R31-2008-000-10103-0] of the Ministry of Education, Science and Technology, Korea (SK) (URL: https://sejong.korea.ac.kr/ mbshome/mbs/eng/subview.do?id=eng_ 040204000000), and funding from The State of Florida to Scripps Florida (MG) (URL: http://www. flgov.com/scripps-florida/). The authors thank Dr. Christopher L. Hendrickson for helpful discussions, Dr. Nathan K. Kaiser and Dr. Donald F. Smith for assistance with operation of mass spectrometers, and John P. Quinn and Dr. Greg T. Blakney for assistance with instrument maintenance and data analysis.
© 2017 Tao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)