The Research Technologies Branch (RTB) Structural Biology Section (SBS) provides specialized techniques and scientific expertise that enables scientists to obtain biophysical and structural data for macromolecules. While closely collaborating with researchers, the SBS provides consulting/training, produces pure proteins, performs biophysical analyses, and determines structures of proteins and other macromolecules.
Biophysical analysis and structural biology require expertise in producing correctly folded proteins at high-purity, in preparing diffraction-quality crystals, and in determining protein structures by X-ray and cryo-EM 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.
Training
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.
Instrumentation
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
The 2.3 Å Structure of A21, a Protein Component of the Conserved Poxvirus Entry-Fusion Complex.
Diesterbeck US, Muslinkina LA, Gittis AG, Singh K, Moss B, and Garboczi DN. (2025). J Mol Biol. Mar 19;437(12):169097. doi: 10.1016/j.jmb.2025.169097.
Chemokines kill bacteria without triggering antimicrobial resistance by binding anionic phospholipids.
Pontejo SM, Martinez S, Zhao A, Barnes K, de Anda J, Alimohamadi H, Lee EY, Dishman AF, Volkman BF, Wong GCL, Garboczi DN, Ballesteros A, Murphy PM. (2025). Sci Adv. Jun 6;11(23):eads2675. doi: 10.1126/sciadv.ads2675. Epub 2025 Jun 6. PMID: 40479071; PMCID: PMC12143392.
Mosquito salivary apyrase regulates blood meal hemostasis and facilitates malaria parasite transmission.
Pala ZR, Alves E Silva TL, Minai M, Crews B, Patino-Martinez E, Carmona-Rivera C, Valenzuela Leon PC, Martin-Martin I, Flores-Garcia Y, Cachau RE, Muslinkina L, Gittis AG, Srivastava N, Garboczi DN, Alves DA, Kaplan MJ, Fischer E, Calvo E, and Vega-Rodriguez J. Nat Commun. 2024 Sep 18;15(1):8194. doi: 10.1038/s41467-024-52502-3. PMID: 39294191; PMCID: PMC11410810.
Structural and immunological differences in Plasmodium falciparum sexual stage transmission-blocking vaccines comprised of Pfs25-EPA nanoparticles.
MacDonald NJ, Singh K, Reiter K, Nguyen V, Shimp R Jr, Gittis AG, Chen B, Burkhardt M, Zhang B, Wang Z, Herrera R, Moler M, Lee DY, Orr-Gonzalez S, Herrod J, Lambert LE, Rausch KM, Muratova O, Jones DS, Wu Y, Jin AJ, Garboczi DN, Duffy PE, Narum DL. NPJ Vaccines. 2023 Apr 15;8(1):56. doi:10.1038/s41541-023-00655-5. PMID: 37061547; PMCID: PMC10105769.
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; PMCID: PMC9662162.
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 Mar28;13(1):1641. doi: 10.1038/s41467-022-29187-7. PMID: 35347133; PMCID:PMC8960830.
Access
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).
Leadership
David Garboczi, Ph.D.
Chief, Structural Biology Section