|
DFG Research Unit FOR 721/2 Molecular Structure and Function of the Tight Junction |
|
|
Project 6 |
Gerd Krause, PhD
, Jörg Piontek, PhD
Structural Bioinformatics & Protein Design, Leibniz Institute of Molecular Pharmacology (FMP), Berlin-Buch
Molecular and structural patterns of paracellular pores by subtype-dependent claudin-claudin interactions in tight junctions
The molecular and structural relation of the claudin-claudin interaction of the different claudin subtypes and their specific function (i.e. pore formation and/or tightness) in the tight junctions is still unsettled. We utilise disparities in pore formation and sequence differences of claudin subtypes in order to characterise molecular and structural patterns of paracellular interactions regarding pore formation and tightness. We combine methods of bioinformatics, molecular biology, mutation tests, and NMR structure tests.
Our starting hypotheses for sealing (structure sample No. I) and for pore-forming (structure sample No. II) of claudins are based mainly on electrostatic attraction and/or repulsion of intermolecular side chain interactions of the extracellular loops 1 (ECL1). Molecular determinants of pore-formation of the ECL1 will be investigated by use of locally arranged chimeric mutations, which are generated from homologous structure models of extracellular loop complexes.
Structural patterns of interacting ECL1 loops will be discovered by applying NMR methods on ECL1 constructs of pore-forming and non-pore-forming claudin subtypes and their complexes.
Granted by project 6
Dr. Anna Veshnyakova (→ Dr. Anna Piontek)
Jonas Protze (doctoral fellow)
2015
Conrad MP*, Piontek J* (*shared first authorship), Günzel D, Fromm M, Krug SM (2016, online 2015) Molecular basis of claudin-17 anion selectivity. Cell. Mol. Life Sci. 73(1): 185-200 (°IF 5.8) [PubMed] [WebPage] [PDF] [Supplement] TP1+TP6+TP7
Protze J, Eichner M, Piontek A, Dinter S, Rossa J, Blecharz KG, Vajkoczy P, Piontek J*, Krause G* (*shared last authorship) (2014) Directed structural modification of Clostridium perfringens enterotoxin to enhance binding to claudin-5. Cell. Mol. Life Sci. ###: ###-### (IF 5.9) [PubMed] [WebPage] [PDF]
Rossa J, Plöger C, Vorreiter F, Saleh T, Protze J, Günzel D, Wolburg H, Krause G, Piontek J (2014) Claudin-3 and claudin-5 protein folding and assembly into the tight junction are controlled by non-conserved residues in transmembrane2 (TM3) and extracellular loop 2 (ECL2) segments. J. Biol. Chem. 289(11): 7641-7653 (IF 4.7) [29.01.14 Accepted] [PubMed] [WebPage] [PDF] [Supplements] TP6+TP7
Rossa J*, Protze J* (*shared first authorship), Kern C, Piontek A, Günzel D, Krause G*, Piontek J* (*shared last authorship) (2014) Molecular and structural transmembrane determinants critical for embedding claudin-5 into tight junctions reveal distinct four helix bundle arrangement. Biochem. J. 464(1): 49-60 (IF 4.8) [PubMed] [WebPage] [PDF]
Cording J, Berg J, Käding N, Bellmann C, Tscheik C, Westphal JK, Milatz S, Günzel D, Wolburg H, Piontek J, Huber O, Blasig IE (2013) Tight junctions: Claudins regulate the interactions between occludin, tricellulin and marvelD3, which, inversely, modulate the claudin oligomerization. J. Cell Sci. 126: 554-564 (IF 6.1) [PubMed] [WebPage] [PDF] [Supplement] TP5+TP7+TP6+TP3
Bal MS*, Castro V* (*shared first autorship), Piontek J, Rueckert C, Walter JK, Shymanets A, Kurig B, Haase H, Nürnberg B, Blasig IE (2012) The hinge region of the scaffolding protein of cell contacts, zonula occludens protein regulates interacting with various signaling proteins. J. Cell. Biochem. 113(3): 934-945 (IF 3.1) [PubMed] [WebPage] [PDF]
Kaufmann R, Piontek J, Grüll F, Kirchgessner M, Rossa J, Wolburg H, Blasig IE, Cremer C (2012) Visualization and quantitative analysis of reconstituted tight junctions using localization microscopy. PLoS One 7(2): e31128 (IF 4.1) [PubMed] [WebPage] [PDF]
Rossa J, Lorenz D, Ringling M, Veshnyakova A, Piontek J (2012) Overexpression of claudin-5 but not claudin-3 induces formation of transinteraction-dependent multilamellar bodies. Ann. N.Y. Acad. Sci. 1257: 59-66 (IF 3.2) [PubMed] [WebPage] [PDF] (Original paper)
Veshnyakova A, Krug SM, Mueller SL, Piontek J, Protze J, Fromm M, Krause G (2012) Determinants contributing to claudin ion channel formation. Ann. N.Y. Acad. Sci. 1257: 45-53 (IF 3.2) [PubMed] [WebPage] [PDF] (Original paper)
Veshnyakova A*, Piontek J*° (*shared first authorship, °corresponding author), Protze J, Waziri N, Heise I, Krause G (2012) Mechanism of Clostridium perfringens enterotoxin interaction with claudin-3/-4 suggests structural modifications of the toxin to target specific claudin. J. Biol. Chem. 287(3): 1698-1708 (IF 5.3) [PubMed] [WebPage] [Full text + supplements PDF]
Walther W, Petkov S, Kuvardina ON, Aumann J, Kobelt D, Fichtner I, Lemm M, Piontek J, Blasig IE, Stein U, Schlag PM (2012) Novel Clostridium perfringens enterotoxin suicide gene therapy for selective treatment of claudin-3- and -4-overexpressing tumors Gene Ther. 19(5): 494-503 (IF 3.7) [PubMed] [WebPage] [PDF]
Piontek J, Fritzsche S, Cording J, Richter S, Hartwig J, Walter M, Yu D, Turner JR, Gehring C, Rahn HP, Wolburg H, Blasig IE (2011) Elucidating the principles of the molecular organization of heteropolymeric tight junction strands. Cell. Mol. Life Sci. 68(23): 3903-3918 [PubMed] [WebPage] [PDF]
Markov AG*, Veshnyakova A* (*shared first authorship), Fromm M, Amasheh M, Amasheh S (2010) Segmental expression of claudin proteins correlates with tight junction barrier properties in rat intestine. J. Comp. Physiol. B 180(4): 591-598 [PubMed] [WebPage] [PDF]
Piehl C,* Piontek J* (*shared first authorship), Cording J, Wolburg H, Blasig IE (2010) Participation of the second extracellular loop of claudin-5 in paracellular tightening against ions, small and large molecules. Cell. Mol. Life Sci. 67(12): 2131-2140 [PubMed] [WebPage] [PDF]
Veshnyakova A, Protze J, Rossa J, Blasig IE, Krause G, Piontek J (2010) On the interaction of clostridium perfringens enterotoxin with claudins. Toxins 2(6): 1336-1356 (review) [Abstract] [PDF]
Westphal JK, Dörfel MJ, Krug SM, Cording JD, Piontek J, Blasig IE, Tauber R, Fromm M, Huber O (2010) Tricellulin forms homomeric and heteromeric tight junctional complexes. Cell. Mol. Life Sci. 67(12): 2057-2068 [PubMed] [WebPage] [Supplement] [PDF]
Zhang J, Piontek J, Wolburg H, Piehl C, Liss M, Otten C, Christ A, Willnow TE, Blasig IE, Abdelilah-Seyfried S (2010) Establishment of a
neuroepithelial barrier by claudin-5a is essential for zebrafish brain ventricular lumen expansion.
Proc. Natl. Acad. Sci.
107(4): 1425-1430 [PubMed] [WebPage] [PDF] Review
Haseloff RF, Piontek J, Blasig IE (2010) The investigation of cis- and trans-interactions between claudins. Curr. Top. Membr. 65: 97-112 [Directory] [WebPage] [PDF] (review / book chapter)
Publications 2007 - 2009 (FOR 721/1)
Walter JK, Castro V, Voss M, Gast K, Rueckert C, Piontek J, Blasig IE (2009) Redox-sensitivity of the dimerization of occludin. Cell. Mol. Life Sci. 66(22): 3655-3662 [PubMed] [WebPage] [PDF]
Krause G, Winkler L, Piehl C, Blasig I, Piontek J, Müller SL (2009) Structure and function of extracellular claudin domains. Ann. N.Y. Acad. Sci. 1165: 34-43 [PubMed] [WebPage] [PDF]
Schillinger C, Boisguerin P, Krause G (2009) Domain Interaction Footprint: a multi-classification approach to predict domain-peptide interactions. Bioinformatics 25(13):1632-1639 [PubMed] [WebPage] [PDF]
Winkler L, Gehring C, Wenzel A, Müller SL, Piehl C, Krause G, Blasig IE*, Piontek J* (*shared last authorship) (2009) Molecular determinants of the interaction between clostridium perfringens enterotoxin fragments and claudin-3. J. Biol. Chem. 284(28): 18863-18872 [PubMed] [WebPage] [PDF]
Krause G, Winkler L, Müller SL, Haseloff RF, Piontek J, Blasig IE (2008) Structure and function of claudins. Biochim. Biophys. Acta 1778(3): 631-645 [PubMed] [WebPage] [PDF]
Piontek J, Winkler L, Wolburg H, Müller SL, Zuleger N, Piehl C, Wiesner B, Krause G, Blasig IE (2008) Formation of tight junction: determinants of homophilic interaction between classic claudins. FASEB J. 22(1): 146-158 [PubMed] [WebPage] [Full paper PDF]
Markov AG, Veshnyakova A, Krug SM, Milatz S (2007) Expression of tight junction proteins in the epithelium of small intestine of the rat. Russ. J. Physiol. (Ross. Fiziol. Zh. Im. I. M. Sechenova) 93(9): 1043-1054 [PubMed]
Previous work
Appelt C, Wessolowski A, Soederhaell JA, Dathe M, Schmieder P (2005) Structure of the antimicrobial, cationic hexapeptide cyclo(RRWWRF) and its analogs in solution and bound to detergent micelles. ChemBioChem 6: 1654-1662.
Ball LJ, Kühne R, Schmieder P, Hoffmann B, Volkmer-Engert R, Schneider-Mergener J, Haefner A, Hof M, Wahl M, Walter U, Oschkinat H, Jarchau T (2000)Dual epitope recognition by the VASP EVH1 domain modulates polyproline ligand specificity and binding affinity. EMBO J. 19: 4903-4914.
Blasig IE, Winkler L, Lassowski B, Mueller SL, Zuleger N, Krause E, Krause G, Gast K, Kolbe M, Piontek J (2006) On the self-association potential of transmembrane tight junction proteins. Cell Mol. Life Sci. 63(4): 505-514.
Brockmann C, Diehl A, Rehbein K, Strauss H, Schmieder P, Korn B, Kühne R, Oschkinat H (2004) The oxidized subunit b8 from human complex I adopts a thioredoxin fold. Structure 12: 1645-1654.
Fujita Y, Krause G, Scheffner M, Zechner D, Leddy HE, Behrens J, Sommer T, Birchmeier W (2002) Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex. Nat. Cell Biol. 4(3): 222-231.
Gaiser OJ, Ball LJ, Schmieder P, Leitner D, Strauss H, Wahl M, Kühne R, Oschkinat H, Heinemann U, (2004) Solution Structure, Backbone Dynamics, and Association Behavior of the C-Terminal BRCT Domain from the Breast Cancer-Associated Protein BRCA1. Biochemistry 43: 15983-15995.
Kahmann JD, Wecking DA, Putter V, Lowenhaupt K, Kim YG, Schmieder P, Oschkinat H, Rich A, Schade M (2004) The solution structure of the N-terminal domain of E3L shows a tyrosine conformation that may explain its reduced affinity to Z-DNA in vitro, Proc. Natl. Acad. Sci. USA 101: 2712-2717 .
Karges B*, Krause G* (*shared first authorship), Homoki J, Debatin KM, deRoux N, Karges W (2005) TSH receptor mutation V509A causes familiar hyperthyroidism by release of interhelical constraints between TMH3-TMH5. J. Endocrinol. 186: 377-385.
Kelly MJS, Ball LJ, Krieger C, Yu Y, Fischer M, Schiffmann S, Schmieder P, Kühne R, Bermel W, Aacher A, Richter G, Oschkinat H (2001) The NMR structure of the 47 kDa dimeric enzyme 3,4-dihydroxy-2-butanone-4-phosphate synthase and the ligand binding studies reveal the location of the active site. Proc. Natl. Acad. Sci. USA 98: 13025-13030.
Kleinau G, Jaschke H, Neumann S, Lattig J, Paschke R, Krause G (2004) Identification of a novel epitope in the thyroid-stimulating hormone receptor ectodomain acting as intramolecular signaling interface. J. Biol. Chem. 279(49): 51590-51600.
Krause G, Hermosilla R, Oksche A, Rutz C, Rosenthal W, Schülein R (2000) Molecular and conformational features of a transport-relevant domain The C-terminal tail of the vasopressin V(2) receptor. Mol. Pharmacol. 57(2): 232-242.
Leitner D, Wahl M, Labudde D, Krause G, Diehl A, Schmieder P, Pires JR, Fossi M, Wiedemann U, Leidert M, Oschkinat H (2005) The solution structure of an N-terminally truncated version of the yeast CDC24p PB1 domain shows a different beta-sheet topology”. FEBS Lett. (2005) 579: 3534-3538.
Mueller SL, Portwich M, Schmidt A, Utepbergenov DI, Huber O, Blasig IE, Krause G (2005) The tight junction protein occludin and the adherens junction protein alpha-catenin share a common interaction mechanism with ZO-1. J. Biol. Chem. 280(5): 3747-3756.
Neumann S, Krause G, Chey S, Paschke R (2001) A free carboxylate oxygen in the side chain of position 674 in transmembrane domain 7 is necessary for TSH receptor activation. Mol. Endocrinol. 15(8): 1294-1305.
Patzelt H, Simon B, terLaak A, Kessler B, Kühne R, Schmieder P, Oesterhelt D, Oschkinat H (2002) The structure of the active center in dark-adapted Bacteriorhodopsin by solution-state NMR spectroscopy”. Proc. Natl. Acad. Sci. USA 99: 9765-9770.
Schade M, Turner CJ, Kühne R, Schmieder P, Lowenhaupt, K,Herbert A, Rich A, Oschkinat H (1999) The solution structure of the Za domain of the human RNA editing enzyme ADAR1 reveals a prepositioned binding surface for Z-DNA". Proc. Natl. Acad. Sci. USA 96: 12465-12470.
Schleinkofer K, Wiedemann U, Otte L, Wang T, Krause G, Oschkinat H, Wade RC (2004) Comparative structural and energetic analysis of WW domain-peptide Interactions. J. Mol. Biol. 344(3): 865-881.
Schmidt A, Utepbergenov DI, Krause G, Blasig IE (2001) Use of surface plasmon resonance for real-time analysis of the interaction of ZO-1 and occludin. Biochem. Biophys. Res. Commun. 288(5): 1194-1199.
Schmidt A, Utepbergenov DI, Krause G, Blasig IE (2003) Direct demonstration of association between the blood-brain barrier proteins ZO-1 and occludin using surface plasmon resonance spectroscopy – effect of SIN-1. In: Blood-Spinal Cord Barriers in Health and Disease. Sharma HS, Westman J (Eds.), Academic Press Elsevier, 11-17.
Schmidt A, Utepbergenov DI, Mueller SL, Beyermann M, Schneider-Mergener J, Krause G, Blasig IE (2004) Occludin binds to the SH3-hinge-GuK unit of zonula occludens protein 1: potential mechanism of tight junction regulation. Cell Mol. Life Sci. 61(11): 1354-1365.
Schubert M, Kolbe M, Kessler B, Oesterhelt D, Schmieder P (2002) Heteronuclear multidimensional NMR-spectroscopy of solubilized membrane proteins: Resonance assignment of native bacteriorhodopsin”. ChemBioChem 3: 1019-1023.
Schultz J Hoffmüller U, Krause G, Ashurst J, Macias MJ, Schmieder P, Schneider-Mergener J, Oschkinat H (1998) Specific interactions between the syntrophin PDZ domain and voltage gated sodium channels. Nat. Struct. Biol. 5: 19-24.
Schülein R, Zühlke K, Krause G, Rosenthal W (2001) Functional rescue of the nephrogenic diabetes insipidus-causing vasopressin V2 receptor mutants G185C and R202C by a second site suppressor mutation. J. Biol. Chem. 276(11): 8384-8392.
Smalla M, Schmieder P, Kelly M, ter Laak A, Krause G, Ball L, Wahl M, Bork P, Oschkinat H (1999) Solution structure of the receptor tyrosine kinase EphB2 SAM domain and identification of two distinct homotypic interaction sites". Prot. Sci. 8: 1954-1961.
Tunaru S, Lättig J, Kero J, Krause G, Offermanns S (2005) Characterization of determinants of ligand binding in the nicotinic acid receptor GPR109A (HM74A/PUMA-G). Mol. Pharmacol. 68(5):1271-1280.
Wiedemann U, Boisguerin P, Leben R, Leitner D, Krause G, Mölling K, Volkmer-Engert R, Oschkinat H (2004) Quantification of PDZ domain specificity, prediction of ligand affinity and rational design of super-binding peptides. J. Mol. Biol. 343: 703-718.
Wüller S, Wiesner B, Löffler A, Furkert J, Krause G, Hermosilla R, Schaefer M, Schülein R, Rosenthal W, Oksche A (2004) Pharmacochaperones post-translationally enhance cell surface expression by increasing conformational stability of wild-type and mutant vasopressin V2 receptors. J. Biol. Chem. 279: 47254-47263.