Designing Cyclic Oligomers: Greater than the Sum of Their Parts
December 5, 2016
A strategy was developed that designs interfaces onto idealized proteins aimed to direct their assembly into multimeric complexes. Researchers used structural characterization, both X-ray crystallography and small angle X-ray scattering (SAXS), to show that many of the designs adopted the target oligomerization state and predicted structure. Not only does the work demonstrate that scientists have a basic understanding of what determines oligomerization, but that they could design proteins with tunable shape, size, and symmetry for a variety of biological applications.
Fallas, J. A., et al. “Computational Design of Self-Assembling Cyclic Protein Homo-Oligomers.” Nat. Chem. 9, 353–360 (2017). [DOI:10.1038/nchem.2673].
Instruments and Facilities Used: Crystallography Collective program; beamline 5.0.2; small angle X-ray scattering (SAXS) on the SIBYLS BL12.3.1 beamline. Advanced Photon Source synchrotron beamline 24-ID-C at Berkeley Center for Structural Biology and Advanced Light Source at Lawrence Berkeley National Laboratory (LBNL).
Funding Acknowledgements: Support: Howard Hughes Medical Institute (HHMI), Air Force Office for Scientific Research (AFOSR FA950-12-10112), National Science Foundation (NSF MCB-1445201 and CHE-1332907), Bill and Melinda Gates Foundation (OPP1120319), and U.S. Department of Defense (DoD) Defense Threat Reduction Agency (HDTRA1-11-C-0026 AM06). R. Koga and L. Carter: assistance with size exclusion chromatography with multi-angle light scattering SEC-MALS. M. Collazo and M. Sawaya support: U.S. Department of Energy (DOE; Grant DE-FC02-02ER63421). M. Capel, K. Rajashankar, N. Sukumar, J. Schuermann, I. Kourinov, and F. Murphy at Northeastern Collaborative Access Team support: grants from National Center for Research Resources (5P41RR015301-10) and National Institutes of Health’s (NIH) National Institute of General Medical Sciences (NIGMS; P41GM103403-10). Use of Advanced Photon Source (APS), Argonne National Laboratory (ANL), support: Office of Biological and Environmental Research (OBER), DOE Office of Science, under Contract DE-AC02-06CH11357. X-ray crystallography and SAXS data collected at the Advanced Light Source (ALS, LBNL, Berkeley, CA, DOE Office of Science contract no. DE-AC02-05CH11231); SAXS data collected through the SIBYLS mail-in SAXS program under aforementioned contract no. and funded by DOE OBER Integrated Diffraction Analysis Technologies (IDAT), NIH Minocycline to Improve Neurologic Outcome in Stroke (MINOS; RO1GM105404), and ALS (K. Burnett and G. Hura). Berkeley Center for Structural Biology (BCSB) support in part: NIH NIGMS and HHMI. ALS support: Office of Basic Energy Sciences (OBES), Director, DOE Office of Science, under contract no. DE-AC02-05CH11231.