Abstract
As an incoming IUPAB Councilor, I have been asked to write a short commentary describing myself and my career in science. Throughout my scientific life, my interests have evolved from initially trying to understand the physical and chemical properties of small molecules toward unraveling biological systems. To that end, I now apply biophysical, biochemical and chemistry tools. Along my journey, I developed and applied nuclear magnetic resonance (NMR) spectroscopy methods to figure out how proteins work at the atomic level and this voyage took me from Germany, where I earned degrees in Physics and Chemistry, to the UK and back to Germany, finally dropping anchor in the USA, where I have led research programs at both the National Institutes of Health and the University of Pittsburgh. I am now the UPMC Rosalind Franklin Professor and Chair of the Department of Structural Biology, University of Pittsburgh School of Medicine, a Professor of Bioengineering, Swanson School of Engineering, and a Professor of Chemistry, Dietrich School of Arts and Sciences, University of Pittsburgh.
References
Bewley CA, Gustafson KR, Boyd MR, Covell DG, Bax A, Clore GM, Gronenborn AM (1998) Solution structure of cyanovirin-N, a potent HIV-inactivating protein. Nat Struct Biol 5:571–578. https://doi.org/10.1038/828
Boatz JC, Whitley MJ, Li M, Gronenborn AM, van der Wel PCA (2017) Cataract-associated P23T gammaD-crystallin retains a native-like fold in amorphous-looking aggregates formed at physiological pH. Nat Commun 8:15137. https://doi.org/10.1038/ncomms15137
Byeon IJ, Ahn J, Mitra M, Byeon CH, Hercik K, Hritz J, Charlton LM, Levin JG, Gronenborn AM (2013) NMR structure of human restriction factor APOBEC3A reveals substrate binding and enzyme specificity. Nat Commun 4:1890. https://doi.org/10.1038/ncomms2883
Cai M, Zheng R, Caffrey M, Craigie R, Clore GM, Gronenborn AM (1997) Solution structure of the N-terminal zinc binding domain of HIV-1 integrase.[erratum appears in Nat Struct Biol 1997 Oct;4(10):839–40]. Nat Struct Biol 4:567–577. https://doi.org/10.1038/nsb0797-567
Campos-Olivas R, Aziz R, Helms GL, Evans JN, Gronenborn AM (2002) Placement of 19F into the center of GB1: effects on structure and stability. FEBS Lett 517:55–60. https://doi.org/10.1016/s0014-5793(02)02577-2
Clore GM, Gronenborn AM (1983) Theory of the time dependent transferred nuclear Overhauser effect: application to the structural analysis of ligand-protein complexes in solution. J Magn Reson 53. https://doi.org/10.1016/0022-2364(83)90215-9
Clore GM, Gronenborn AM (1985) The solution structure of a B-DNA undecamer comprising a portion of the specific target site for the cAMP receptor protein in the gal operon. Refinement on the basis of interproton distance data. EMBO J 4:829–835. https://doi.org/10.1002/j.1460-2075.1985.tb03705.x
Clore GM, Gronenborn AM (1989) Determination of three-dimensional structures of proteins and nucleic acids in solution by nuclear magnetic resonance spectroscopy. Crit Rev Biochem Mol Biol 24:479–564. https://doi.org/10.3109/10409238909086962
Clore GM, Gronenborn AM (1991) Structures of larger proteins in solution: three- and four-dimensional heteronuclear NMR spectroscopy. Science 252:1390–1399. https://doi.org/10.1126/science.2047852
Clore GM, Gronenborn AM (1998) New methods of structure refinement for macromolecular structure determination by NMR. Proc Natl Acad Sci U S A 95:5891–5898. https://doi.org/10.1073/pnas.95.11.5891
Clore GM, Nilges M, Sukumaran DK, Brunger AT, Karplus M, Gronenborn AM (1986) The three-dimensional structure of alpha1-purothionin in solution: combined use of nuclear magnetic resonance, distance geometry and restrained molecular dynamics. EMBO J 5:2729–2735. https://doi.org/10.1002/j.1460-2075.1986.tb04557.x
Clore GM, Omichinski JG, Sakaguchi K, Zambrano N, Sakamoto H, Appella E, Gronenborn AM (1994) High-resolution structure of the oligomerization domain of p53 by multidimensional NMR. Science 265:386–391. https://doi.org/10.1126/science.8023159
Clore GM, Sukumaran DK, Nilges M, Zarbock J, Gronenborn AM (1987) The conformations of hirudin in solution: a study using nuclear magnetic resonance, distance geometry and restrained molecular dynamics. EMBO J 6:529–537. https://doi.org/10.1002/j.1460-2075.1987.tb04785.x
Fritz M, Kraus J, Quinn CM, Yap GPA, Struppe J, Sergeyev IV, Gronenborn AM, Polenova T (2019) Measurement of accurate interfluorine distances in crystalline organic solids: a high-frequency magic angle spinning NMR approach. J Phys Chem B 123:10680–10690. https://doi.org/10.1021/acs.jpcb.9b08919
Gronenborn AM (2018) Harnessing the combined power of SAXS and NMR. Adv Exp Med Biol 1105:171–180. https://doi.org/10.1007/978-981-13-2200-6_11
Gronenborn AM (2019) Integrated BioNMR — “getting by with a little help from my friends.” J Magn Reson 306:192–194. https://doi.org/10.1016/j.jmr.2019.07.040
Gronenborn AM (2019b) Integrated multidisciplinarity in the natural sciences. J Biol Chem 294:18162–18167. https://doi.org/10.1074/jbc.AW119.008142
Gronenborn AM (2021) Small, but powerful and attractive: 19F in biomolecular NMR. In press, Structure
Gronenborn AM, Birdsall B, Hyde EI, Roberts GCK, Feeney J, Burgen ASV (1981) Direct observation by NMR of two coexisting conformations of an enzyme-ligand complex in solution. Nature 290:273–274. https://doi.org/10.1038/290273a0
Gronenborn AM, Clore GM (1985) Investigations into the solution structures of short nucleic acid fragments by means of nuclear Overhauser enhancement measurements. Prog Nucl Magn Reson Spectrosc 17:1–32. 10.1.1.488.4722
Gronenborn AM, Clore GM, Brunori M, Giardina B, Falcioni G, Perutz MF (1984) Stereochemistry of ATP and GTP bound to fish haemoglobins. A transferred nuclear overhauser enhancement, 31P-nuclear magnetic resonance, oxygen equilibrium and molecular modelling study. J Mol Biol 178:731–742. https://doi.org/10.1016/0022-2836(84)90249-3
Gronenborn AM, Filpula DR, Essig NZ, Achari A, Whitlow M, Wingfield PT, Clore GM (1991) A novel, highly stable fold of the immunoglobulin binding domain of streptococcal protein G. Science 253:657–661. https://doi.org/10.1126/science.1871600
Guseman AJ, Whitley MJ, Gonzalez JJ, Rathi N, Ambarian M, Gronenborn AM (2021) Assessing the structures and interactions of gammaD-crystallin deamidation variants. Structure 29:284.e283-291.e283. https://doi.org/10.1016/j.str.2020.11.006
Kay LE, Clore GM, Bax A, Gronenborn AM (1990) Four-dimensional heteronuclear triple-resonance NMR spectroscopy of interleukin-1 beta in solution. Science 249:411–414. https://doi.org/10.1126/science.2377896
Krzysiak TC, Thomas L, Choi YJ, Auclair S, Qian Y, Luan S, Krasnow SM, Thomas LL, Koharudin LMI, Benos PV et al (2018) Aninsulin-responsive sensor in the SIRT1 disordered region binds DBC1 and PACS-2 to control enzyme activity. Mol Cell 72:985.e987-998.e987. https://doi.org/10.1016/j.molcel.2018.10.007
Lu M, Ishima R, Polenova T, Gronenborn AM (2019a) (19)F NMR relaxation studies of fluorosubstituted tryptophans. J Biomol NMR 73:401–409. https://doi.org/10.1007/s10858-019-00268-y
Lu M, Russell RW, Bryer AJ, Quinn CM, Hou G, Zhang H, Schwieters CD, Perilla JR, Gronenborn AM, Polenova T (2020) Atomic-resolution structure of HIV-1 capsid tubes by magic-angle spinning NMR. Nat Struct Mol Biol 27:863–869. https://doi.org/10.1038/s41594-020-0489-2
Lu M, Wang M, Sergeyev IV, Quinn CM, Struppe J, Rosay M, Maas W, Gronenborn AM, Polenova T (2019b) (19)F dynamic nuclear polarization at fast magic angle spinning for NMR of HIV-1 capsid protein assemblies. J Am Chem Soc 141:5681–5691. https://doi.org/10.1021/jacs.8b09216
Matei E, Gronenborn AM (2016) (19)F paramagnetic relaxation enhancement: a valuable tool for distance measurements in proteins. Angew Chem Int Ed 55:150–154. https://doi.org/10.1002/anie.201508464
Omichinski JG, Clore GM, Sakaguchi K, Appella E, Gronenborn AM (1991) Structural characterization of a 39-residue synthetic peptide containing the two zinc binding domains from the HIV-1 p7 nucleocapsid protein by CD and NMR spectroscopy. FEBS Lett 292:25–30. https://doi.org/10.1016/0014-5793(91)80825-n
Omichinski JG, Clore GM, Schaad O, Felsenfeld G, Trainor C, Appella E, Stahl SJ, Gronenborn AM (1993) NMR structure of a specific DNA complex of Zn-containing DNA binding domain of GATA-1. Science 261:438–446. https://doi.org/10.1126/science.8332909
Perilla JR, Hadden-Perilla JA, Gronenborn AM, Polenova T (2021) Integrative structural biology of HIV-1 capsid protein assemblies: combining experiment and computation. Curr Opin Virol 48:57–64. https://doi.org/10.1016/j.coviro.2021.03.005
Quinn CM, Wang M, Fritz MP, Runge B, Ahn J, Xu C, Perilla JR, Gronenborn AM, Polenova T (2018) Dynamic regulation of HIV-1 capsid interaction with the restriction factor TRIM5alpha identified by magic-angle spinning NMR and molecular dynamics simulations. Proc Natl Acad Sci U S A 115:11519–11524. https://doi.org/10.1073/pnas.1800796115
Sharaf, N.G., and Gronenborn, A.M. (2015). Chapter 4- 19F-modified proteins and 19F-containing ligands as tools in solution NMR studies of protein interactions. In Methods in Enzymology, Z. Kelman, ed. (Academic Press), pp. 67–95. https://doi.org/10.1016/bs.mie.2015.05.014
Sharaf NG, Ishima R, Gronenborn AM (2016) Conformational plasticity of the NNRTI-binding pocket in HIV-1 reverse transcriptase: a fluorine nuclear magnetic resonance study. Biochemistry 55:3864–3873. https://doi.org/10.1021/acs.biochem.6b00113
Wu Y, Zhou X, Barnes CO, DeLucia M, Cohen AE, Gronenborn AM, Ahn J, Calero G (2016) The DDB1-DCAF1-Vpr-UNG2 crystal structure reveals how HIV-1 Vpr steers human UNG2 toward destruction. Nat Struct Mol Biol 23:933–940. https://doi.org/10.1038/nsmb.3284
Xi Z, Whitley MJ, Gronenborn AM (2017) Human betaB2-crystallin forms a face-en-face dimer in solution: an Integrated NMR and SAXS Study. Structure 25:496–505. https://doi.org/10.1016/j.str.2017.02.001
Zhao G, Perilla JR, Yufenyuy EL, Meng X, Chen B, Ning J, Ahn J, Gronenborn AM, Schulten K, Aiken C et al (2013) Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics. Nature 497:643–646. https://doi.org/10.1038/nature12162
Funding
Over the years, research in my laboratory has been supported by the National Science Foundation (currently CHE-1708773 and MCB-BSF-2116534) and the National Institutes of Health (currently R01EY030057, R01DK114855, and P50AI150481).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The author declares no competing interests.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Gronenborn, A.M. Meet the IUPAB councilor — Angela M. Gronenborn. Biophys Rev 13, 835–838 (2021). https://doi.org/10.1007/s12551-021-00886-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12551-021-00886-7