Structural Biology at the Research Technologies Branch (RTB)

The Research Technologies Branch (RTB) Structural Biology Section (SBS) provides specialized techniques and scientific expertise that enables Division of Intramural Research (DIR) scientists to obtain biophysical and structural data for macromolecules. While closely collaborating with DIR researchers, the SBS provides consulting/training, produces pure proteins, performs biophysical analyses, and determines structures of proteins and other macromolecules that are central to the infectious disease and immunology research programs of DIR.

Biophysical analysis and structural biology require expertise in producing correctly folded proteins at high-purity, in preparing diffraction-quality crystals, and in determining crystal structures by X-ray methods. With an emphasis on providing training in biochemical, biophysical, and structural methods, the SBS makes it possible for investigators to use structurally based ideas and techniques in their research programs.

Major Areas of Support

Protein expression expertise

We advise on how to prepare a validated and high-quality protein sample for study. We express and purify proteins to be used in a variety of biochemical and biophysical techniques. We help prepare high-quality protein samples for structural determinations by X-ray and cryo-EM methods.

Light scattering and isothermal titration calorimetry

To estimate the aggregation state of a protein, we use light scattering instruments.  Non-aggregated protein is essential for biochemical assays and for all forms of three dimensional structural studies. Using isothermal titration calorimetry technology, we measure the binding between proteins and their ligands.

Bio-layer interferometry

To measure the affinity of small molecules (drugs) binding to proteins and of the affinity of proteins for each other, we use bio-layer interferometry.

X-ray crystallography

To determine the structure of a protein, of several proteins, or of a protein/RNA/DNA complex, we prepare crystals and use X-ray crystallography.


Our goal is to train investigators in each of the biochemical and biophysical technologies that they need and so allow investigators to understand and use the technologies independently.


The Section performs biophysical analyses including dynamic light scattering, circular dichroism, isothermal titration calorimetry, and biolayer interferometry.

Collaborative Technological Resources

The SBS collaborates in the design of protein constructs and experimental strategies for all projects involving the biochemistry of proteins and their ligands.

Selected Publications

Functional aspects of evolution in a cluster of salivary protein genes from mosquitoes.
Alvarenga PH, Dias DR, Xu X, Francischetti IMB, Gittis AG, Arp G, Garboczi DN, Ribeiro JMC, Andersen JF. Insect Biochem Mol Biol. 2022 Jul;146:103785. doi: 10.1016/j.ibmb.2022.103785. Epub 2022 May 12. PMID: 35568118

Structural basis of R-loop recognition by the S9.6 monoclonal antibody.
Bou-Nader C, Bothra A, Garboczi DN, Leppla SH, Zhang J. Nat Commun. 2022 Mar 28;13(1):1641. doi: 10.1038/s41467-022-29187-7. PMID: 35347133

The structures of two salivary proteins from the West Nile vector Culex quinquefasciatus reveal a beta-trefoil fold with putative sugar binding properties.
Kern O, Valenzuela Leon PC, Gittis AG, Bonilla B, Cruz P, Chagas AC, Ganesan S, Ribeiro JMC, Garboczi DN, Martin-Martin I, Calvo E. Curr Res Struct Biol. 2021 Mar 16;3:95-105. doi: 10.1016/j.crstbi.2021.03.001. eCollection 2021. PMID: 34235489

Aedes aegyptiPiwi4 Structural Features Are Necessary for RNA Binding and Nuclear Localization.
Williams AE, Shrivastava G, Gittis AG, Ganesan S, Martin-Martin I, Valenzuela Leon PC, Olson KE, Calvo E. Int J Mol Sci. 2021 Nov 25;22(23):12733. doi: 10.3390/ijms222312733. PMID: 34884537

Structure and function of a malaria transmission blocking vaccine targeting Pfs230 and Pfs230-Pfs48/45 proteins. Singh K, Burkhardt M, Nakuchima S, Herrera R, Muratova O, Gittis AG, Kelnhofer E, Reiter K, Smelkinson M, Veltri D, Swihart BJ, Shimp R Jr, Nguyen V, Zhang B, MacDonald NJ, Duffy PE, Garboczi DN, Narum DL. Commun Biol. 2020 Jul 24;3(1):395. doi: 10.1038/s42003-020-01123-9. PMID: 32709983

The 2.1 Å structure of protein F9 and its comparison to L1, two components of the conserved poxvirus entry-fusion complex.
Diesterbeck US, Gittis AG, Garboczi DN, Moss B. Sci Rep. 2018 Nov 14;8(1):16807. doi: 10.1038/s41598-018-34244-7. PMID: 30429486


Currently, collaborating with RTB is only available to federally funded institutions. Researchers may access all RTB support services by visiting RTB on Inside NIAID (this link is only available to NIAID lab scientists).


David Garboczi, Ph.D.
Chief, Structural Biology Section

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