Joern Werner and Group

 

Overview


 Joern WernerJörn Werner

 jmwe@soton.ac.uk

Structural changes of proteins are important for the control of cellular processes and failure to function correctly can lead to disease. We are studying the nature of protein-ligand interactions that have well-characterised biological functions with atomic resolution. The role of protein dynamics in molecular recognition processes is a particular focus of my work.

 

 

 

Research


Establishing the developmental function of the pectic component rhamnogalacturonan II (RGII)
Rhamnogalacturonan II is a complex pectic polysaccharide that is an important component of the plant primary cell wall. A molecular genetic based approach is being adopted in Arabidopsis thaliana to identify the key roles of RGII during root development.
The plant primary cell wall is comprised of a complex set of polysaccharides including pectin, cellulose and hemicelluloses that are crucial for normal development. There are 3 major forms of pectin, homogalacturonan (HGA), rhamnogalacturonan I (RGI) and rhamnogalacturonan II (RGII). RGII is the least abundant pectin which has the same glacturonic acid backbone as HGA but is substituted with 4 side chains comprised of 12 different monosaccharides linked by 20 different glycosyl linkages. Some of these monosaccharides including D-apiose, 2-keto-3-deoxy-D-manno-octulosonic acid (Kdo) and 2-keto-3-deoxy-D-lyxo-heptulosaric acid (Dha) are rare in plants and possibly unique to RGII. Although RGII is a low abundance cell wall component, its structure is conserved in all vascular plants suggesting its function is important and that the structure is a critical feature for function. Despite the likely importance of RGII, little is known about its biosynthesis or function.
An ethanol inducible transactivation based system is being used to provide spatial and temporal control of the downregulation of genes involved in the synthesis of CMP-Kdo, an activated precursor that is used as a substrate during RGII biosynthesis. This will allow the role of RGII during specific developmental programmes such as root elongation, root hair formation and lateral root induction to be studied.

People

Dr Halina Mikolayek

Louise Bolton

Kelly Hooper

Publications


 
Pigott, Craig R., Mikolajek, Halina, Moore, Claire E., Finn, Stephen J., Phippen, Curtis W., Werner, Jörn M. and Proud, Christopher G. (2012) Insights into the regulation of eukaryotic elongation factor 2 kinase and the interplay between its domains. Biochemical Journal, 442, (1), 105-118. (doi:10.1042/BJ20111536). (PMID:22115317).
 
Dalchau, Neil, Phillips, Andrew, Goldstein, Leonard D., Howarth, Mark, Cardelli, Luca, Emmott, Stephen, Elliott, Tim and Werner, Joern M. (2011) A peptide filtering relation quantifies MHC class I peptide optimization. PLoS Computational Biology, 7, (10), e1002144-[14pp]. (doi:10.1371/journal.pcbi.1002144). (PMID:22022238).
 
Taylor, Garrick F., Wood, Stephen P., Moers, Karsten, Glaubitz, Clemens, Werner, Jorn M. and Williamson, Phillip T.F. (2011) Morphological differences between beta2-microglobulin in fibrils and inclusion bodies. ChemBioChem, 12, (4), 556-558. (doi:10.1002/cbic.201000582).
 
Leung, Leo, Tomassi, Cyrille, Van Beneden, Katrien, Decruy, Tine, Trappeniers, Matthias, Elewaut, Dirk, Gao, Yifang, Elliott, Tim, Al-Shamkhani, Aymen, Ottensmeier, Christian, Werner, Jörn M., Williams, Anthony, Van Calenbergh, Serge and Linclau, Bruno (2009) The synthesis and in vivo evaluation of 2,2-difluoro KRN7000. ChemMedChem, 4, (3), 329 -334. (doi:10.1002/cmdc.200800348 ).
 
Leung, Leo, Tomassi, Cyrille, Van Beneden, Katrien, Decruy, Tine, Elewaut, Dirk, Elliott, Tim, Al-Shamkhani, Aymen, Ottensmeier, Christian, Van Calenbergh, Serge, Werner, Joern, Williams, Tony and Linclau, Bruno (2008) Synthesis and in vivo evaluation of 4-deoxy-4,4-difluoro-KRN7000. Organic Letters, 10, (20), 4433-4436. (doi:10.1021/ol801663m).
 
Scheschonka, Astrid, Findlow, Stuart C. , Schemm, Rudolf, El Far, Oussama, Caldwell, John H., Crump, Matthew P., Holden-Dye, Kate, O’Connor, Vincent, Betz, Heinrich and Werner, Jorn M. (2008) Structural determinants of calmodulin binding to the intracellular C-terminal domain of the metabotropic glutamate receptor 7A. Journal of Biological Chemistry, 283, (9), 5577-5588. (doi:10.1074/jbc.M709505200 ). (PMID:18089570).
 
El-Sagheer, Afaf H., Kumar, Ravindra, Findlow, Stuart C. , Werner, Joern M., Lane, Andrew N. and Brown, Tom (2008) A very stable cyclic DNA miniduplex with just two base pairs. ChemBioChem, 9, (1), 50-52. (doi:10.1002/cbic.200700538). (PMID:18058775).
 
Rachwal, P.A., Findlow, I.S., Werner, J.M., Brown, T. and Fox, K.R. (2007) Intramolecular DNA quadruplexes with different arrangements of short and long loops. Nucleic Acids Research, 35, (12), 4214-4222. (doi:10.1093/nar/gkm316).
 
Rudino-Pinera, E., Ravelli, R.B.G., Sheldrick, G.M., Nanao, M.H., Korostelev, V.V., Werner, J.M., Schwarz-Linek, U., Potts, J.R. and Garman, E.F. (2007) The solution and crystal structures of a module pair from the Staphylococcus aureus-binding site of human fibronectin – A tale with a twist. Journal of Molecular Biology, 368, (3), 833-844. (doi:10.1016/j.jmb.2007.02.061).
 
Pilka, Ewa S., Werner, Joern M., Schwarz-Linek, Ulrich, Pickford, Andrew R., Meenan, Nicola A.G., Campbell, Iain D. and Potts, Jennifer R. (2006) Structural insight into binding of Staphylococcus aureus to human fibronectin. FEBS Letters, 580, (1), 273-277. (doi:10.1016/j.febslet.2005.12.008).
 
Hofmann, Gregor, Schweimer, Kristian, Kiessling, Anke, Hofinger, Edith, Bauer, Finn, Hoffmann, Silke, Rösch, Paul, Campbell, Iain D., Werner, Jörn M. and Sticht, Heinrich (2005) Binding, domain orientation, and dynamics of the lck SH3-SH2 domain pair and comparison with other Src-family kinases. Biochemistry, 44, (39), 13043-13050. (doi:10.1021/bi050814y).
 
Sticht, Jana, Humbert, Michael, Findlow, Stuart C. , Bodem, Jochen, Müller, Barbara, Dietrich, Ursula, Werner, Jörn and Kräusslich, Hans-Georg (2005) A peptide inhibitor of HIV-1 assembly in vitro. Nature Structural & Molecular Biology, 12, (8), 671-677. (doi:10.1038/nsmb964).
 
Altroff, H., Schlinkert, R., Walle, C.F., Bernini, A., Campbell, I.D., Werner, J.M. and Mardon, H.J. (2004) Interdomain tilt angle determines integrin-dependent function of the ninth and tenth FIII domains of human fibronectin. Journal of Biological Chemistry, 279, (53), 55995-56003. (doi:10.1074/jbc.M406976200).
 
Hambleton, Sophie, Valeyev, Najl V., Muranyi, Andreas, Knott, Vroni, Werner, Jorn M., McMichael, Andrew J., Handford, Penny A. and Downing, A. Kristina (2004) Structural and functional properties of the human Notch-1 ligand binding region.Structure, 12, (12), 2173-2183.
 
Kurniawan, Nyoman D., Leary, Joanne M., Thamlitz, Ann-Marie, Sofair, Raphael, Werner, Jörn M., Stenflo, Johan and Downing, A. Kristina (2004) N-terminal domain linkage modulates the folding properties of protein S epidermal growth factor-like modules. Biochemistry, 43, (29), 9352-9360. (doi:10.1021/bi0492105).
 
Hoellerer, Maria K., Noble, Martin E.M., Labesse, Gilles, Campbell, Iain D., Werner, Jörn M. and Arold, Stefan T. (2003) Molecular recognition of paxillin LD motifs by the focal adhesion targeting domain. Structure, 11, (10), 1207-1217. (doi:10.1016/j.str.2003.08.010).
 
Schwarz-Linek, Ulrich, Werner, Jörn M., Pickford, Andrew R., Gurusiddappa, Sivashankarappa, Kim, Jung Hwa, Pilka, Ewa S., Briggs, John A. G., Gough, T. Sebastian, Höök, Magnus, Campbell, Iain D. and Potts, Jennifer R. (2003) Letter to Nature. Pathogenic bacteria attach to human fibronectin through a tandem beta-zipper. Nature, 423, (6936), 177-181. (doi:10.1038/nature01589).
 
Schwarz-Linek, U., Werner, J.M., Pickford, A.R., Gurusiddappa, S., Kim, J.H., Pilka, E.S., Briggs, J.A.G., Gough, T.S., Hook, M., Campbell, I.D. and Potts, J.R. (2003) Pathogenic bacteria attach to human fibronectin through a tandem beta-zipper. Nature, 423, 177-181. (doi:10.1038/nature01589).
 
Smallridge, R.S., Whiteman, P., Werner, J.M., Campbell, I.D., Handford, P.A. and Downing, A.K. (2003) Solution structure and dynamics of a calcium binding epidermal growth factor-like domain pair from the neonatal region of human fibrillin-1. Journal of Biological Chemistry, 278, (14), 12199-12206. (doi:10.1074/jbc.M208266200).
 
Ulmer, T.S., Werner, J.M. and Campbell, I.D. (2002) SH3-SH2 domain orientation in Src kinases: NMR studies of Fyn.Structure, 10, (Jul), 901-911.
Yuan, X.M., Werner, J.M., Lack, J., Knott, V., Handford, P.A., Campbell, I.D. and Downing, A.K. (2002) Effects of the N2144S mutation on backbone dynamics of a TB-cbEGF domain pair from human fibrillin-1. Journal of Molecular Biology, 316, (1), 113-125. (doi:10.1006/jmbi.2001.5329).
 
Saha, S., Boyd, J., Werner, J.M., Knott, V., Handford, P.A., Campbell, I.D. and Downing, A.K. (2001) Solution structure of the LDL receptor EGF-AB pair: A paradigm for the assembly of tandem calcium binding EGF domains.Structure, 9, (6), 451-456.
 
Arold, S.T., Ulmer, T.S., Mulhern, T.D., Werner, J.M., Ladbury, J.E., Campbell, I.D. and Noble, M.E.M. (2001) The role of the Src homology 3-Src homology 2 interface in the regulation of Src kinases. Journal of Biological Chemistry, 276, (20), 17199-17205. (doi:10.1074/jbc.M011185200).

Additional publications

El-Sagheer AH, Kumar R, Findlow IS, Werner JM, Lane AN and Brown T. (2008) A Very stable cyclic DNA mini-duplex with just two base pairs, Chembiochem, 9, 50-52.

Werner, J.M. , Knott, V., Handford, P.A., Campbell, I.D. & Downing, A.K. (2000) Backbone dynamics of a cbEGF domain pair in the presence of calcium. J.Mol.Biol., 296, 1065-1078.

Hashimoto, Y., Smith, S.P., Pickford, A.R., Bocquier, A.A., Campbell, I.D. & Werner, J.M. (2000) The relative orientation of the fibronectin 6F1 1F2 module pair: A 15N NMR relaxation study. J.Biomol.NMR., 17, 203-214.

Smith, S.P., Hashimoto, Y., Pickford, A.R., Campbell, I.D. & Werner, J.M. (2000) Interface characterisation of the type II module pair from fibronectin. Biochemistry, 39, 8374-8381.

 

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