Center for Structural Biology
The newly formed Center for Structural Biology (CSB) will serve as the focus for structural biology activities across the CCR. The Center's foundation is built from the merger of the Structural Biophysics Laboratory and the Macromolecular Crystallography Laboratory.
The Center will: 1) plan, develop and conduct research studies on the molecular structure and interactions of biological macromolecules and therapeutics pertinent to human health, with a particular emphasis on cancer and infection; 2) support training of personnel in advanced structural methods; 3) develop and apply new tools for molecular characterization using novel biophysical and biochemical techniques including cryo-electron microscopy, nuclear magnetic resonance (NMR) spectroscopy, x-ray diffraction and scattering methods; 4) lead methods development to enable full understanding of large, multi-component molecular machines; and 5) apply structural and chemical insights to develop mechanistic understanding to inform therapeutics strategies.
PI & Key Staff
The Center for Structural Biology offers several resources to CCR and other NIH intramural investigators.
The Biophysics Resource (BR), operated by the Center, provides CCR investigators with access to both the latest instrumentation and expertise in characterizing the biophysical aspects of systems under structural investigation.
The Biophysics Resource operates as an open, shared-use facility; in general, BR users learn to operate the instruments and conduct their own experients. Our staff members train all first-time users and are also available to consult with investigators on experimental design/analysis or collaborate with them on more complex studies. To learn more, visit the Biophysics Resource.
The mission of the SAXS Core Facility is to provide support to research projects from CCR principal investigators (PIs), NIH intramural PIs and extramural academic research groups and laboratories. The support includes providing routine access to the APS PUP SAXS/WAXS beamline and in-house SAXS instrument, and expertise in experimental design, data collection, processing, analysis and interpretation. Our main focus is to determine the structure of biomacromolecules and their complexes in solution. The research field includes, but is not limited to, structural studies of nucleic acids, proteins, protein assemblies, virus particles, lipid membranes, protein/DNA and protein/RNA complexes. To learn more, visit the SAXS Core Facility.
NMR Facility for Biological Research
Within the Center is a state-of-the-art nuclear magnetic resonance (NMR) facility that researchers use to solve atomic resolution three-dimensional (3D) structures, probe molecular dynamics, and aid in structure-based drug design and molecular targeting. The facility is managed by Dr. Janusz Koscielniak, who is an expert in NMR spectrometer hardware and software. The instruments have been used to study how nucleic acids bind inhibitors, define new functional interaction sites in biomachines, and to reveal structural and dynamic properties critical to biological function.
NMR Selected Recent Publications
A sampling of recent publications from the NMR Facility is presented below.
Ding, J., Swain, M., Yu, P., Stagno, J. R., Wang, Y. X. Conformational flexibility of adenine riboswitch aptamer in apo and bound states using NMR and an X-ray free electron laser. J. Biomol. NMR., Sep;73(8-9):509-518, 2019. PMID: 31606878 PMCID: PMC6817744
Biancospino, M., Buel, G. R., Niño, C. A., Maspero, E., di Perrotolo, R. S., Raimondi, A., Redlingshöfer, L., Weber, J., Brodsky, F. M.*, Walters, K. J.*, Polo, S.* Clathrin light chain A drives selective myosin VI recruitment to clathrin-coated pits under membrane tension. Nature Communications, 10(1):4974, 2019. doi: 10.1038/s41467-019-12855-6. *co-corresponding. PMID: 31672988 PMCID: PMC6823378
Chao, F.-A., Li, Y., Zhang, Y., Byrd, R.A. Probing the broad time scale and heterogeneous conformational dynamics in the catalytic core of the Arf-GAP ASAP1 via methyl adiabatic relaxation dispersion. J. Am. Chem. Soc., 141(30):11881-11891, 2019. PMID: 31293161
Solomon, W.C., Myint, W., Hou, S., Kanai, T., Tripathi, R., Yilmaz, N.K., Schiffer, C.A., Matsuo H. Mechanism for APOBEC3G catalytic exclusion of RNA and non-substrate DNA. Nucleic Acids Research, 47(14):7676-7689, 2019. PMID: 31424549 PMCID: PMC6698744
Liu, Y., Holmstrom, E., Yu, P., Tan, K., Zuo, X., Nesbitt, D. J., Sousa, R., Stagno, J. R., Wang, Y. X. Incorporation of isotopic, fluorescent, and heavy-atom-modified nucleotides into RNAs by position-selective labeling of RNA. Nat Protoc., May;13(5):987-1005, 2018. PMID: 29651055
Calabrese, D. R., Chen, X., Leon, E., Gaikwad, S., Phyo, Z., Hewitt, W. M., Alden, S., Hilimire, T. A., He, F., Michalowski, A. M., Simmons, J. K., Saunders, L. B., Zhang, S., Connors, D., Walters, K. J.*, Mock, B. A.*, Schneekloth, J. S. Jr.* Chemical and structural studies provide a mechanistic basis for recognition of the MYC G-quadruplex. Nature Communications, 9:4229, 2018. doi: 10.1038/s41467-018-06315-w. *co-corresponding. PMID: 30315240 PMCID: PMC6185959
Maiti A, Myint W, Kanai T, Delviks-Frankenberry K, Sierra Rodriguez C, Pathak VK, Schiffer CA, Matsuo H. Crystal structure of the catalytic domain of HIV-1 restriction factor APOBEC3G in complex with ssDNA. Nature Communications, Jun 25;9(1):2460, 2018. PMID: 29941968 PMCID: PMC6018426
There are several seminar series available to staff members interested in structural biology and/or molecular discovery.
Structural Biology Seminar Series
All seminars in the Center for Structural Biology series will be help from 3-4PM in the main auditorium of the B549 Conference Center.
Nov 18, 2022 Filippo Mancia, Columbia University
Dec 2, 2022 TBD
Dec 16, 2022 Karen Fleming, Johns Hopkins University
Jan 13, 2023 TBD
Jan 27, 2023 Kenji Murakami, University of Pennsylvania
Feb 10, 2023 Tony Hunter, Salk Institute
Feb 24, 2023 Francesca Marassi, Medical College of Wisconsin
Mar 10, 2023 John Gross, University of California San Francisco
Mar 24, 2023 Deb Kelly, Penn State University
Apr 21, 2023 Jenny Hinshaw, National Institute of Diabetes and Digestive and Kidney Diseases
May 5, 2023 Edward Marcotte, University of Texas
May 19, 2023 Bill Clemons, California Institute of Technology
CBL Molecular Discovery Seminar Series
View the Molecular Discovery Seminar Series, sponsored by the Chemical Biology Laboratory (CBL).
Center for Cancer Research National Cancer Institute
- Building 538, Room 213
- Frederick, MD 21702-1201