Gerhard Wagner

Gerhard Wagner

Elkan Rogers Blout Professor of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
Gerhard Wagner

Our research is focused on protein structure, dynamics and stability, and on the relation of these to protein function using NMR and computational techniques as the main tools used to address these problems.We are interested in improving NMR methods and techniques to make proteins suitable for structural studies.

We seek to understand mechanisms of T-cell function from structural studies. To this end, we have solved the solution structures of the human T-cell adhesion glycoprotein CD2 and its counter receptor CD58. Both proteins need to by glycosylated to be functional. When examining the role of the glycans we designed mutants that eliminate the need for glycosylation. This was possible , the glycan-free mutants behave well and enabled us to solve the CD2/CD58 complex. We also have solved the structure of the Fv fragment of a class II-specific abTCR and the egCD3 heterodimer. We are interested in the mechanisms of TCR signaling, which involves interactions between the clonotypic abTCR, the invariant CD3 components of the TCR and cytoplasmic proteins.

Another focus in the laboratory is on eukaryotic translation initiation.  In particular, we are interested in the interaction of eIF4E with the mRNA cap and with eIF4G. We are also working on other factors involved in eukaryotic translation initiation, such as eIF2 and eIF2B and sIF5B. We are also interested in identifying small molecules that inhibit translation initiation.

We are also interested in protein-protein interactions that are relevant for apoptosis. In the past, we have studied the caspase-recruitment domains of RAIDD and Apaf-1, the regulatory domains of CIDE, DFF40 and DFF45 and their mutual complexes.  Furthermore, we are have recently determined the structure the BID protein that is relevant for promoting mitochondrial damage in apoptosis. Recently, we became interested in identifying small-molecule inhibitors of antiapoptotic proteins, such as Bcl-xL, and to investigate their effect on cell growth.

Selected Publications:

S. Imai, P.Kumar, C.U.T. Hellen, V. D’Souza, G.Wagner: An accurately pre-organized IRES RNA structure enables eIF4G capture for initiating viral translation. Nature Structural and Molecular Biology, 23(9):859-864. doi: 10.1038/nsmb.3280 (2016). PMC5061125

M.L. Nasr, D. Baptista, M.Strauss, Z.-Y. J. Sun, S. Grigoriu, S. Huser, A. Plückthun, F. Hagn,, T. Walz, J. M. Hogle, G. Wagner : Covalently circularized nanodiscs for studying membrane proteins and viral entry, Nature Methods. 2016 Nov 21. doi: 10.1038/nmeth.4079. PMID: 27869813, PMC5199620

K. Takeuchi, H. Arthanari, G. Wagner: Perspective: revisiting the field dependence of TROSY sensitivity. J Biomol NMR. 2016 Dec;66(4):221-225. doi: 10.1007/s10858-016-0075-4. PMC5218892.

Z.J. Sun, M.K. Bhanu, M.G. Allan, H.Arthanari, G. Wagner, J. Hanna. Solution Structure of the Cuz1 AN1 Zinc Finger Domain: An Exposed LDFLP Motif Defines a Subfamily of AN1 Proteins. PLoS One. 2016 Sep 23;11(9). doi: 10.1371/journal.pone.0163660 PMC5035049

P. Coote, W. Bermel, G. Wagner, H. Arthanari . Analytical optimization of active bandwidth and quality factor for TOCSY experiments in NMR spectroscopy. J Biomol NMR. Sep;66(1):9-20 (2016) doi: 10.1007/s10858-016-0051-z PMC5175489

Das DK, Mallis RJ, Duke-Cohan JS, Hussey RE, Tetteh PW, Hilton M, Wagner G, Lang MJ, Reinherz EL. Pre-T Cell Receptors (Pre-TCRs) Leverage Vβ Complementarity Determining Regions (CDRs) and Hydrophobic Patch in Mechanosensing Thymic Self-ligands. J Biol Chem. 2016 Dec 2;291(49):25292-25305. Epub 2016 Oct 5. PMC5207233

Contact Information

Harvard Medical School, Building C1, Room 112
240 Longwood Avenue, Boston, MA 02115
p: 617 432-3213

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