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1ff1

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Revision as of 07:46, 23 February 2022

STRUCTURE OF THE SECOND EPS15 HOMOLOGY DOMAIN OF HUMAN EPS15 IN COMPLEX WITH PTGSSSTNPFL

Structural highlights

1ff1 is a 2 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1eh2, 1f8h
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[EPS15_HUMAN] Note=A chromosomal aberration involving EPS15 is found in acute leukemias. Translocation t(1;11)(p32;q23) with MLL/HRX. The result is a rogue activator protein.

Function

[EPS15_HUMAN] Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role in the assembly of clathrin-coated pits (CCPs). Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2.^[1] ^[2] ^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Eps15 homology (EH) domains are protein interaction modules that recognize Asn-Pro-Phe (NPF) motifs in their biological ligands to mediate critical events during endocytosis and signal transduction. To elucidate the structural basis of the EH-NPF interaction, the solution structures of two EH-NPF complexes were solved using NMR spectroscopy. The first complex contains a peptide representing the Hrb C-terminal NPFL motif; the second contains a peptide in which an Arg residue substitutes the C-terminal Leu. The NPF residues are almost completely embedded in a hydrophobic pocket on the EH domain surface and the backbone of NPFX adopts a conformation reminiscent of the Asx-Pro type I beta-turn motif. The residue directly following NPF is crucial for recognition and is required to complete the beta-turn. Five amino acids on the EH surface mediate specific recognition of this residue through hydrophobic and electrostatic contacts. The complexes explain the selectivity of the second EH domain of Eps15 for NPF over DPF motifs and reveal a critical aromatic interaction that provides a conserved anchor for the recognition of FW, WW, SWG and HTF ligands by other EH domains.

Molecular mechanism of NPF recognition by EH domains.,de Beer T, Hoofnagle AN, Enmon JL, Bowers RC, Yamabhai M, Kay BK, Overduin M Nat Struct Biol. 2000 Nov;7(11):1018-22. PMID:11062555^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Roxrud I, Raiborg C, Pedersen NM, Stang E, Stenmark H. An endosomally localized isoform of Eps15 interacts with Hrs to mediate degradation of epidermal growth factor receptor. J Cell Biol. 2008 Mar 24;180(6):1205-18. doi: 10.1083/jcb.200708115. PMID:18362181 doi:10.1083/jcb.200708115
↑ Mettlen M, Stoeber M, Loerke D, Antonescu CN, Danuser G, Schmid SL. Endocytic accessory proteins are functionally distinguished by their differential effects on the maturation of clathrin-coated pits. Mol Biol Cell. 2009 Jul;20(14):3251-60. doi: 10.1091/mbc.E09-03-0256. Epub 2009, May 20. PMID:19458185 doi:10.1091/mbc.E09-03-0256
↑ Teckchandani A, Mulkearns EE, Randolph TW, Toida N, Cooper JA. The clathrin adaptor Dab2 recruits EH domain scaffold proteins to regulate integrin beta1 endocytosis. Mol Biol Cell. 2012 Aug;23(15):2905-16. doi: 10.1091/mbc.E11-12-1007. Epub 2012, May 30. PMID:22648170 doi:10.1091/mbc.E11-12-1007
↑ Schmid EM, Ford MG, Burtey A, Praefcke GJ, Peak-Chew SY, Mills IG, Benmerah A, McMahon HT. Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly. PLoS Biol. 2006 Sep;4(9):e262. PMID:16903783 doi:http://dx.doi.org/10.1371/journal.pbio.0040262
↑ de Beer T, Hoofnagle AN, Enmon JL, Bowers RC, Yamabhai M, Kay BK, Overduin M. Molecular mechanism of NPF recognition by EH domains. Nat Struct Biol. 2000 Nov;7(11):1018-22. PMID:11062555 doi:10.1038/80924

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1ff1"

@@ Line 3: / Line 3: @@
 <StructureSection load='1ff1' size='340' side='right'caption='[[1ff1]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1ff1]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FF1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FF1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1ff1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FF1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FF1 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1eh2|1eh2]], [[1f8h|1f8h]]</div></td></tr>
@@ Line 35: / Line 35: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Beer, T De]]

1ff1

From Proteopedia

Revision as of 07:46, 23 February 2022

STRUCTURE OF THE SECOND EPS15 HOMOLOGY DOMAIN OF HUMAN EPS15 IN COMPLEX WITH PTGSSSTNPFL

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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