Advertisement

Journal of Biomolecular NMR

, Volume 39, Issue 4, pp 323–329 | Cite as

EH domain of EHD1

  • Fabien Kieken
  • Marko Jović
  • Naava Naslavsky
  • Steve Caplan
  • Paul L. Sorgen
NMR Structure Note

Abstract

EHD1 is a member of the mammalian C-terminal Eps15 homology domain (EH) containing protein family, and regulates the recycling of various receptors from the endocytic recycling compartment to the plasma membrane. The EH domain of EHD1 binds to proteins containing either an Asn-Pro-Phe or Asp-Pro-Phe motif, and plays an important role in the subcellular localization and function of EHD1. Thus far, the structures of five N-terminal EH domains from other proteins have been solved, but to date, the structure of the EH domains from the four C-terminal EHD family paralogs remains unknown. In this study, we have assigned the 133 C-terminal residues of EHD1, which includes the EH domain, and solved its solution structure. While the overall structure resembles that of the second of the three N-terminal Eps15 EH domains, potentially significant differences in surface charge and the structure of the tripeptide-binding pocket are discussed.

Keywords

EHD1 EH domain 

Notes

Acknowledgements

This work was supported by grants from the National Institutes of Health (GM072631, P.L.S.; GM074876, S.C.), the UNMC Eppley Cancer Center Collaborative Research Award (P.L.S. and S.C.), and the Nebraska Center for Cell Signaling fellowship supported by the National Institutes of Health (P20 RR018759, M.J.).

References

  1. Brunger AT, Adams PD, Clore GM, DeLano WL, Gros P, Grosse-Kunstleve RW, Jiang JS, Kuszewski J, Nilges M, Pannu NS, Read RJ, Rice LM, Simonson T, Warren GL (1998) Crystallography & NMR system: a new software suite for macromolecular structure determination. Acta Crystallogr D Biol Crystallogr 54(Pt 5):905–921CrossRefGoogle Scholar
  2. Caplan S, Naslavsky N, Hartnell LM, Lodge R, Polishchuk RS, Donaldson JG, Bonifacino JS (2002) A tubular EHD1-containing compartment involved in the recycling of major histocompatibility complex class I molecules to the plasma membrane. EMBO J 21:2557–2567CrossRefGoogle Scholar
  3. Confalonieri S, Di Fiore PP (2002) The Eps15 homology (EH) domain. FEBS Lett 513:24–29CrossRefGoogle Scholar
  4. de Beer T, Carter RE, Lobel-Rice KE, Sorkin A, Overduin M (1998) Structure and Asn-Pro-Phe binding pocket of the Eps15 homology domain. Science 281:1357–1360CrossRefADSGoogle Scholar
  5. de Beer T, Hoofnagle AN, Enmon JL, Bowers RC, Yamabhai M, Kay BK, Overduin M (2000) Molecular mechanism of NPF recognition by EH domains. Nat Struct Biol 7:1018–1022CrossRefGoogle Scholar
  6. Delaglio F, Grzesiek S, Vuister GW, Zhu G, Pfeifer J, Bax A (1995) NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J Biomol NMR 6:277–293CrossRefGoogle Scholar
  7. Johnson BAaB R A. (1994) NMRView: a computer program for the visualization and analysis of NMR data. J Biomol NMR 4:603–614CrossRefGoogle Scholar
  8. Jovic M, Naslavsky N, Rapaport D, Horowitz M, Caplan S (2007) EHD1 regulates beta1 integrin endosomal transport: effects on focal adhesions, cell spreading and migration. J Cell Sci 120:802–814CrossRefGoogle Scholar
  9. Kay LE, Forman-Kay JD, McCubbin WD, Kay CM (1991) Solution structure of a polypeptide dimer comprising the fourth Ca(2+)-binding site of troponin C by nuclear magnetic resonance spectroscopy. Biochemistry 30:4323–4333CrossRefGoogle Scholar
  10. Koradi R, Billeter M, Wuthrich K (1996) MOLMOL: a program for display and analysis of macromolecular structures. J Mol Graph 14:51–55, 29–32Google Scholar
  11. Laskowski RA, Rullmannn JA, MacArthur MW, Kaptein R, Thornton JM (1996) AQUA and PROCHECK-NMR: programs for checking the quality of protein structures solved by NMR. J Biomol NMR 8:477–486CrossRefGoogle Scholar
  12. Lin SX, Grant B, Hirsh D, Maxfield FR (2001) Rme-1 regulates the distribution and function of the endocytic recycling compartment in mammalian cells. Nat Cell Biol 3:567–572CrossRefGoogle Scholar
  13. Linge JP, O’Donoghue SI, Nilges M (2001) Automated assignment of ambiguous nuclear overhauser effects with ARIA. Methods Enzymol 339:71–90CrossRefGoogle Scholar
  14. Linge JP, Williams MA, Spronk CA, Bonvin AM, Nilges M (2003) Refinement of protein structures in explicit solvent. Proteins 50:496–506CrossRefGoogle Scholar
  15. Naslavsky N, Boehm M, Backlund PS Jr, Caplan S (2004) Rabenosyn-5 and EHD1 interact and sequentially regulate protein recycling to the plasma membrane. Mol Biol Cell 15:2410–2422CrossRefGoogle Scholar
  16. Naslavsky N, Caplan S (2005) C-terminal EH-domain-containing proteins: consensus for a role in endocytic trafficking, EH? J Cell Sci 118:4093–4101CrossRefGoogle Scholar
  17. Naslavsky N, Rahajeng J, Sharma M, Jovic M, Caplan S (2006) Interactions between EHD proteins and Rab11-FIP2: a role for EHD3 in early endosomal transport. Mol Biol Cell 17:163–177CrossRefGoogle Scholar
  18. Naslavsky N, Rahajeng J, Chenavas S, Sorgen PL, Caplan S (2007) EHD1 and Eps15 Interact with phosphatidylinositols via their Eps15 homology domains. J Biol Chem 282:16612–16622CrossRefGoogle Scholar
  19. Strynadka NC, James MN (1989) Crystal structures of the helix-loop-helix calcium-binding proteins. Annu Rev Biochem 58:951–998CrossRefGoogle Scholar
  20. Whitehead B, Tessari M, Carotenuto A, van Bergen en Henegouwen PM, Vuister GW (1999) The EH1 domain of Eps15 is structurally classified as a member of the S100 subclass of EF-hand-containing proteins. Biochemistry 38:11271–11277CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular Biology and Eppley Cancer CenterUniversity of Nebraska Medical CenterOmahaUSA

Personalised recommendations