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DFG-Forschergruppe FOR 721/2 Molekulare Struktur und Funktion der Tight Junction |
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Teilprojekt 6 |
Dr.
Gerd Krause
, Dr. Jörg
Piontek
Leibniz-Institut für Molekulare Pharmakologie (FMP), Berlin-Buch
Molekulare und strukturelle Muster parazellulärer Dichtheit durch subtypabhängige Claudin-Claudin-Wechselwirkungen in Tight Junctions
Der molekulare und strukturelle Zusammenhang der Claudin-Claudin-Interaktion zwischen diversen Claudinsubtypen und deren unterschiedlicher Funktion (Porenbildung bzw. Dichtheit) in den Tight Junctions ist noch ungeklärt. Unter gezielter Ausnutzung von unterschiedlicher Porenbildungsfunktion und Sequenzunterschieden der Claudinsubtypen sollen systematisch molekulare und strukturelle Muster parazellulärer Wechselwirkungen für Porenbildung und Dichtheit durch Kombination von bioinformatischen, molekularbiologischen, Mutationen- und NMR-Strukturuntersuchungen eingegrenzt und identifiziert werden.
Unsere Starthypothesen für
abdichtende (Strukturmuster I) und für parazellulär porenbildende
(Strukturmuster II) Interaktionsmuster von Claudinsubtypen basieren u.a. auf
elektrostatischer Anziehung bzw. Abstoßung von intermolekularen
Seitenketteninteraktionen der extrazellulären Loops 1 (ECL1).
Mit gezielten ortgerichteten Chimären-Mutationen, die aus weiteren homologen
Strukturmodellen extrazellulärer Loop Komplexe gewonnen werden, sollen
porenbildende molekulare Determinanten in den ECL1 der Claudine iterativ
eingegrenzt werden.
Strukturmuster wechselwirkender ECL1-Loops sollen durch NMR-Strukturaufklärung von ECL1-Konstrukten von porenbildenden und nicht-porenbildenden Claudinsubtypen und deren Komplexe gewonnen werden.
DFG-Mitarbeiter des Teilprojekts
Dr. Anna Veshnyakova
Jonas Protze (Doktorand)
Publikationen 2010 - 2012 (FOR 721/2)
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] [HTML] [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 (2012) Tight junctions: Claudins regulate the interactions between occludin, tricellulin and marvelD3, which, inversely, modulate the claudin oligomerization. J. Cell Sci. ###: ###-### (IF 6.1) [PubMed] [WebPage] [PDF] TP5+TP7+TP6+TP3
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)
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] [HTML] [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] [HTML] [PDF]
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] [HTML] [Full text + supplements 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] [HTML] [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] [HTML] [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] [HTML] [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]
[HTML] [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] [HTML] [PDF] (review / book chapter)
Publikationen 2007 - 2009 (FOR 721/1)
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] [HTML] [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] [HTML] [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] [HTML] [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] [HTML] [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] [HTML] [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]
Vorarbeiten
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.