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Teachers Abstracts – Section for Biomolecular Sciences - University of Copenhagen

Summer School 2008 > Teachers Abstracts

Talk titles and materials for round table discussions:

Final list - updated June 3rd 10.30 am

Vicente Rubio

Talk title: "One fold, several architectures and lots of functions. The Amino acid kinase family as an example"

Round table discussion: "Increasing structural and functional complexity of a single enzyme: catalysis of phosphoryl group transfer, allosteric regulation and signaling through macromolecular complex formation"

1. Ramón-Maiques S, Marina A, Gil-Ortiz F, Fita I, Rubio V. (2002) Structure of acetylglutamate kinase, a key enzyme for arginine biosynthesis and a prototype for the amino acid kinase enzyme family, during catalysis. Structure. 10(3):329-42.

2. Gil-Ortiz F, Ramón-Maiques S, Fita I, Rubio V. (2003) The course of phosphorus in the reaction of N-acetyl-L-glutamate kinase, determined from the structures of crystalline complexes, including a complex with an AlF4- transition state mimic. J Mol Biol. 331:231-44.

3. Ramón-Maiques S, Fernández-Murga ML, Gil-Ortiz F, Vagin A, Fita I, Rubio V. (2006) Structural bases of feed-back control of arginine biosynthesis, revealed by the structures of two hexameric N-acetylglutamate kinases, from Thermotoga maritima and Pseudomonas aeruginosa. J Mol Biol. 356:695-713.

4. Llácer JL, Contreras A, Forchhammer K, Marco-Marín C, Gil-Ortiz F, Maldonado R, Fita I, Rubio V. (2007) The crystal structure of the complex of PII and acetylglutamate kinase reveals how PII controls the storage of nitrogen as arginine. Proc Natl Acad Sci U S A. 104:17644-9.  

Christian Griesinger

Title of talk and round table discussion: "Recognition of globular proteins: Conformational selection at 100 ns
time scale?" 

1. Lakomek NA, Carlomagno T, Becker S, Griesinger C, Meiler J. "A thorough dynamic interpretation of residual dipolar couplings in ubiquitin." J Biomol NMR. 2006 Feb;34(2):101-15.

2. Lakomek NA, Farès C, Becker S, Carlomagno T, Meiler J, Griesinger C."Side-chain orientation and hydrogen-bonding imprint supra-Tau(c) motion on the protein backbone of ubiquitin." Angew Chem Int Ed Engl. 2005 Dec 2;44(47):7776-8

3. Peti W, Meiler J, Brüschweiler R, Griesinger C. "Model-free analysis of protein backbone motion from residual dipolar couplings." J Am Chem Soc. 2002 May 22;124(20):5822-33.

4. Meiler J, Prompers JJ, Peti W, Griesinger C, Brüschweiler R. "Model-free approach to the dynamic interpretation of residual dipolar couplings in globular proteins." J Am Chem Soc. 2001 Jun 27;123(25):6098-107.

5. Clore GM, Schwieters CD. "How much backbone motion in ubiquitin is required to account for dipolar coupling data measured in multiple alignment media as assessed by independent cross-validation?" J Am Chem Soc. 2004 Mar 10;126(9):2923-38.

6. Markwick PR, Bouvignies G, Blackledge M. "Exploring multiple timescale motions in protein GB3 using accelerated molecular dynamics and NMR spectroscopy." J Am Chem Soc. 2007 Apr 18;129(15):4724-30

7. Bouvignies G, Bernadó P, Meier S, Cho K, Grzesiek S, Brüschweiler R, Blackledge M. "Identification of slow correlated motions in proteins using residual dipolar and hydrogen-bond scalar couplings." Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13885-90.

8. Bax A, Grishaev A. "Weak alignment NMR: a hawk-eyed view of biomolecular structure." Curr Opin Struct Biol. 2005 Oct;15(5):563-70. Review.

9. Goh CS, Milburn D, Gerstein M. "Conformational changes associated with protein-protein interactions." Curr Opin Struct Biol. 2004 Feb;14(1):104-9. Review. 

Rolf Boelens

Talk title: "Structure and dynamics of DNA binding proteins and of photosensory systems"

van der Horst MA, Hellingwerf KJ. "Photoreceptor proteins, "star actors of modern times": a review of the functional dynamics in the structure of representative members of six different photoreceptor families". Acc Chem Res. 2004 Jan;37(1):13-20. Review.

Kalodimos CG, Boelens R, Kaptein R."Toward an integrated model of protein-DNA recognition as inferred from NMR studies on the Lac repressor system". Chem Rev. 2004 Aug;104(8):3567-86. Review

Croteau DL, Peng Y, Van Houten B. "DNA repair gets physical: Mapping an XPA-binding site on ERCC1".DNA Repair (Amst). 2008 May 3;7(5):819-26. Epub 2008 Mar 14.

KJ. Hellingwerf, J. Hendriks and T. Gensch. "Photoactive Yellow Protein, A New Type of Photoreceptor Protein: Will This "Yellow Lab" Bring Us Where We Want to Go?"J. Phys. Chem. A, (2003) 107 (8), 1082 -1094.

Round Table discussion:

1. Tripsianes K, Folkers GE, Zheng C, Das D, Grinstead JS, Kaptein R, Boelens R. "Analysis of the XPA and ssDNA-binding surfaces on the central domain of human ERCC1 reveals evidence for subfunctionalization". Nucleic Acids Res. 2007;35(17):5789-98. Epub 2007 Aug 24.

2. Bernard C, Houben K, Derix NM, Marks D, van der Horst MA, Hellingwerf KJ, Boelens R, Kaptein R, van Nuland NA. "The solution structure of a transient photoreceptor intermediate: Delta25 photoactive yellow protein". Structure. 2005 Jul;13(7):953-62. 

3. Tripsianes K, Folkers G, Ab E, Das D, Odijk H, Jaspers NG, Hoeijmakers JH, Kaptein R, Boelens R."The structure of the human ERCC1/XPF interaction domains reveals a complementary role for the two proteins in nucleotide excision repair". Structure. 2005 Dec;13(12):1849-58.  

Sachdev Sidhu

Talk title: Synthetic antibodies as antagonists and agonists of cell signaling

1. Fellouse FA, Esaki K, Birtalan S, Raptis D, Cancasci VJ, Koide A, Jhurani P, Vasser M, Wiesmann C, Kosiakoff AA, et al.: High-throughput generation of synthetic antibodies from highly functional minimalist phage-displayed libraries. J. Mol. Biol. 2007, 373:924-940.

2. Fellouse FA, Li B, Compaan DM, Peden AA, Hymowitz SG, Sidhu SS: Molecular recognition by a binary code. J. Mol. Biol. 2005, 348:1153-1162.

3. Fellouse FA, Wiesmann C, Sidhu SS: Synthetic antibodies from a four-amino-acid code: a dominant role for tyrosine in antigen recognition. Proc. Natl. Acad. Sci. USA 2004, 101:12467-12472.

4. Li B, Russell SJ, Compaan DM, Totpal K, Marsters SA, Ashkenazi A, Cochran AG, Hymowitz SG, Sidhu SS: Activation of the proapoptotic death receptor DR5 by oligomeric peptide and antibody agonists. J. Mol. Biol. 2006, 361:522-536.

Round Table Discussion: Phage-displayed antibodies

1. Brekke OH, Loset GA: New technologies in therapeutic antibody development. Curr. Opin. Pharmacol. 2003, 3:544-550.

2. Chambers RS: High-throughput antibody production. Curr. Opin. Chem. Biol. 2004, 9:46-50.

3. Hoogenboom HR: Selecting and screening recombinant antibody libraries. Nature Biotechnol. 2005, 23:1105-1116.

4. Sidhu SS, Fellouse FA: Synthetic therapeutic antibodies. Nature Chem. Biol. 2006, 2:682-688.

Mikael Akke

Talk title and Round table discussion: "Enzyme catalysis and ligand binding from a physical chemist's perspective" 

1. Ma B, Kumar S, Tsai C-J, Nussinov R. (1999) Prot. Eng. 12, 713-720. "Folding funnels and binding mechanisms."

2. Boehr DD, McElheny D, Dyson HJ, Wright PE. (2006) Science 313, 1638-1642. "The dynamic energy landscape of dihydrofolate reductase catalysis."

Tobin Sosnick

Talk title: "Quantifying the structural requirements of the folding transition state"

Sosnick, T. R., Krantz, B. A., Dothager, R. S. & Baxa, M. Characterizing the Protein Folding Transition State Using psi Analysis. Chem. Rev. 106, 1862-76 (2006).

Pandit, A. D., Jha, A., Freed, K. F. & Sosnick, T. R. Small Proteins Fold Through Transition States With Native-like Topologies. J. Mol. Biol. 361, 755-70 (2006).

Round table discussion: "What is important for /ab initio /protein structure prediction?"

1. Ozkan, S. B., Wu, G. A., Chodera, J. D. & Dill, K. A. Protein folding by zipping and assembly. Proc. Natl. Acad. Sci. U S A 104, 11987-11992 (2007).

2. Colubri, A. et al. Minimalist Representations and the Importance of Nearest Neighbor Effects in Protein Folding Simulations. J. Mol. Biol. 363, 835-857 (2006).

Dorothee Kern


Round table discussion: "Exploration of protein's dynamic personalities by biophysical tools"

1. Henzler-Wildman KA. and Kern D. "Dynamic personalities of proteins" Nature (2007) 450, 964-972

2. Henzler-Wildman KA, Thai V, Lei M, Ott M, Wolf-Watz M, Fenn T, Pozharski E, Wilson MA, Petsko GA, Karplus M, Hübner CG, Kern D." Intrinsic motions along an enzymatic reaction trajectory." Nature (2007) 450, 838-844.

3. Henzler-Wildman KA, Lei M, Thai V, Kerns SJ, Karplus M, Kern D. "A hierarchy of timescales in protein dynamics is linked to enzyme catalysis." Nature (2007), 450: 913-916.

4. Palmer, A. G. NMR characterization of the dynamics of biomacromolecules. Chem. Rev. 104, 3623-3640 (2004).

5. Eisenmesser, E.Z., Millet, O., Labeikovsky, W., Korzhnev, D.M., Wolf-Watz, M., Bosco, D.A., Skalicky, J.J., Kay, L.E. and Kern, D. "Intrinsic dynamics of an enzyme underlies catalysis" Nature (2005), 438, 117-121

6. Volkman, B.F., Lipson, D., Wemmer, D.E. and Kern, D. "Two-state allosteric behavior in a single-domain signaling protein" Science 291, 2429-2433 (2001).

Jacob Anglister 

Talk title: "NMR studies of the interactions of bungarotoxin with the acetylcholine receptor and of Interferon with its receptor."

Round table discussion: "NMR studies of Receptor-Ligand interactions"

1. Sun, C., Song, D., Davis-Taber, R. A., Barrett, L. W., Scott, V. E., Richardson, P. L., Pereda-Lopez, A., Uchic, M. E., Solomon, L. R., Lake, M. R., Walter, K. A., Hajduk, P. J., and Olejniczak, E. T. (2007) Solution structure and mutational analysis of pituitary adenylate cyclase-activating polypeptide binding to the extracellular domain of PAC1-RS, Proc Natl Acad Sci USA 104, 7875-7880.

2. Veldkamp, C. T., Seibert, C., Peterson, F. C., Sakmar, T. P., and Volkman, B. F. (2006) Recognition of a CXCR4 sulfotyrosine by the chemokine stromal cell-derived factor-1alpha (SDF-1alpha/CXCL12), J Mol Biol 359, 1400-14092.

3. Huang, C. C., Lam, S. N., Acharya, P., Tang, M., Xiang, S. H., Hussan, S. S., Stanfield, R. L., Robinson, J., Sodroski, J., Wilson, I. A., Wyatt, R., Bewley, C. A., and Kwong, P. D. (2007) Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4, Science 317, 1930-1934.

4. Quadt-Akabayov, S. R., Chill, J. H., Levy, R., Kessler, N., and Anglister, J. (2006) Determination of the human type I interferon receptor binding site on human interferon-alpha2 by cross saturation and an NMR-based model of the complex, Protein Sci 15, 2656-2668.

5. Inooka, H., Ohtaki, T., Kitahara, O., Ikegami, T., Endo, S., Kitada, C., Ogi, K., Onda, H., Fujino, M., and Shirakawa, M. (2001) Conformation of a peptide ligand bound to its G-protein coupled receptor, Nat Struct Biol 8, 161-165. 

Sheena E Radford

Talk tile: "Sequence specific effects and the mechanism of amyloid formation"

Round Table Discussion: "Towards new therapeutic routes for amyloid."

1. Martins IC et al. "Lipids revert inert Abeta amyloid fibrils to neurotoxic protofibrils that affect learning in mice." EMBO J. 2008 27(1):224-33.

2. Luheshi LM et al. "Systematic in vivo analysis of the intrinsic determinants of amyloid Beta pathogenicity." PLoS Biol. 2007 5(11):e290.

3. Sekjima, Y et al. "The biological and chemical basis for tissue-selective amyloid disease." Cell. 2005 121(1):73-85

Alan Berry

Title of talk: "New enzyme activities by directed evolution".

Round Table discussion: 

1. Desai & Gallivan "Genetic Screens and Selections for Small Molecules Based on a Synthetic Riboswitch That Activates Protein Translation". (2004) J. Am . Chem. Soc. 126, 13247-54

2. Rothlisberger et al. "Kemp elimination catalysts by computational enzyme design". (2008) Nature 453, 190-197

3. Mehl et al. "Generation of a Bacterium with a 21 Amino Acid Genetic Code". (2003) J Am Chem Soc 125, 935-939

Christina Redfield

Title of talk: "Using NMR spectroscopy to study molten globule states of proteins -
examples from alpha-lactalbumin and apomyoglobin"

C. Redfield, Using NMR spectroscopy to study molten globule states of proteins, Methods 34, 121-132 (2004).

H.J. Dyson and P.E. Wright, Unfolded Proteins and Protein Folding Studied by NMR, Chemical Reviews 104(8), 3607-3622 (2004).

Round table discussion: For the round table discussion I will continue on the theme of NMR studies of molten globules but will widen the topic to include other examples. The two reviews listed above will be relevant. In addition, I would suggest:

1. Pervushin, K et al., Structure and dynamics of a molten globule enzyme, Nature Structural and Molecular Biology 14(12) 1202-1206 (2007).

2. Li, H and Frieden, C, Fluorine-19 NMR studies on the acid state of the intestinal fatty acid binding protein, Biochemistry 45 6272-6278 (2006).

3. Schwarzinger, S et al., Structural characterization of partially folded intermediates of apomyoglobin H64F, Protein Science 17 313-321 (2008).

Birthe B. Kragelund

Title of talk and round table discussion: "Functional aspects of protein flexibility in hormone-receptor interaction"

Stroud RM, Wells JA. "Mechanistic diversity of cytokine receptor signaling across cell membranes." Sci STKE. 2004 Apr 28;2004(231):

Teilum K, Hoch JC, Goffin V, Kinet S, Martial JA, Kragelund BB. "Solution structure of human prolactin." J Mol Biol. 2005 Aug 26;351(4):810-23.

Round table discussion
1. Brown RJ, Adams JJ, Pelekanos RA, Wan Y, McKinstry WJ, Palethorpe K, Seeber RM, Monks TA, Eidne KA, Parker MW, Waters MJ. "Model for growth hormone receptor activation based on subunit rotation within a receptor dimer." Nat Struct Mol Biol. 2005 Sep;12(9):814-21.

2. Weidemann T, Höfinger S, Müller K, Auer M. "Beyond dimerization: a membrane-dependent activation model for interleukin-4 receptor-mediated signalling". J Mol Biol. 2007 Mar 9;366(5):1365-73

3. Ballinger MD, Wells JA. "Will any dimer do?" Nat Struct Biol. 1998 Nov;5(11):938-40

Kaare Teilum

Title of talk: "Early conformational events in protein misfolding."

Chiti, F. & Dobson, C. M. (2006). Protein misfolding, functional amyloid, and human disease. Annu. Rev. Biochem. 75, 333-366. Review

Round table discussion: "Toxicity of misfolded protein. Are the oligomers always to blame?"

1. Engel, M. F. M., Khemtemourian, L., Kleijer, C. C., Meeldijk, H. J. D., Jacobs, J., Verkleij, A. J., de Kruijff, B., Killian, J. A. & Hoppener, J. W. M. (2008). Membrane damage by human islet amyloid polypeptide through fibril growth at the membrane. Proc Natl Acad Sci USA 105, 6033-6038.

2. Brender, J. R., Lee, E. L., Cavitt, M. A., Gafni, A., Steel, D. G. & Ramamoorthy, A. (2008). Amyloid Fiber Formation and Membrane Disruption are Separate Processes Localized in Two Distinct Regions of IAPP, the Type-2-Diabetes-Related Peptide. J. Am. Chem. Soc. 130, 6424-6429.

3. Quist, A., Doudevski, I., Lin, H., Azimova, R., Ng, D., Frangione, B., Kagan, B., Ghiso, J. & Lal, R. (2005). Amyloid ion channels: a common structural link for protein-misfolding disease. Proc Natl Acad Sci USA 102, 10427-32.

4. Kayed, R., Head, E., Thompson, J. L., McIntire, T. M., Milton, S. C., Cotman, C. W. & Glabe, C. G. (2003). Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 300, 486-489.

Peter Roepstorff

Talk title: "The use of mass spectrometry for studies of protein interaction, folding and aggregation."

"Sequencing of entire genomes culminating with the human genome and those of several plants of has changed the perspectives of modern biological science. Now in the post genome era functional genomics is becoming a buzz-word. This rather vague term involves studies of the expression and function of gene products on all levels. Proteomics is one of the key analytical tools in functional genomics and mass spectrometry the key instrumentation. Proteomics is performed on three levels:
  - Expression proteomics, i.e., which genes are expressed when and where?
  - Modification specific proteomics, i.e., which modified variants are present of each         protein?
  - Cell map proteomics or interactomics, i.e., who interacts with who, when and how?
We are in our research group performing proteomics studies on all three levels. Since we have the hypothesis that protein modifications are used in the living organism to regulate interactions and their kinetics, we want to investigate the interdependence between protein modification and protein interaction. In order to perform such studies we have developed a number of mass spectrometry based methods to study protein interaction. These include:
  - Pull-down of interacting proteins followed by identification of interacting partners using a   proteomics approach.
  - Studies of interaction kinetics by combining surface plasmon resonance (BIA-technology)   with mass spectrometry
  - Identification of the boundaries of the interaction interface by surface labelling and       cross-linking followed by analysis by MS.
  - Studies of the interaction interface by deuterium exchange mass spectrometry.
The present state of art of these different techniques will be illustrated using examples from our ongoing projects."

Round table discussions:  "The use of mass spectrometry for studies of protein interaction, folding and aggregation."

1. Benedetta Mattei, Jonas Borch, Peter Roepstorff. "Surface plasmon resonance coupled with MS is a practical tool for identifying and characterizing protein interactions." Article send by email

2. Jonas Borch, Thomas JD Jørgensen and Peter Roepstorff, Mass spectrometric analysis of protein interactions, Current Opinion in Chemical Biology (2005), 9: 5, 509-516  

3. Heegaard NH, Jørgensen TJ, Rozlosnik N, Corlin DB, Pedersen JS, Tempesta AG, Roepstorff P, Bauer R, Nissen MH. Unfolding, aggregation, and seeded amyloid formation of lysine-58-cleaved beta 2-microglobulin.Biochemistry. 2005 Mar 22;44(11):4397-407.

4. Jørgensen TJ, Gårdsvoll H, Danø K, Roepstorff P, Ploug M. Dynamics of urokinase receptor interaction with Peptide antagonists studied by amide hydrogen exchange and mass spectrometry.Biochemistry. 2004 Nov 30;43(47):15044-57.