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2ftu

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2ftu, 20 NMR models ()
Gene: LRPAP1 (Homo sapiens)
Related: 2fft, 2ffv
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

solution structure of domain 3 of RAP

Publication Abstract from PubMed

The receptor associated protein (RAP) is an antagonist and molecular chaperone that binds tightly to low-density lipoprotein receptor family members in the endoplasmic reticulum (ER). After escorting these receptors to the Golgi, RAP dissociates from the receptors. The molecular mechanism of the dissociation has been unknown until now. The solution structure of RAP-D3 domain presented here reveals a striking increase in positively charged residues on the surface of this RAP domain due to protonation of solvent-exposed histidine sidechains as the pH is reduced from a near neutral pH of the ER to the acidic pH of the Golgi. Structure-based mutagenesis studies in vitro and in cells confirm that the protonation of histidine residues as a consequence of the pH changes modulate the binding/release of RAP from LRP. This histidine switch may serve as a general mechanism for regulating cell trafficking events.

RAP uses a histidine switch to regulate its interaction with LRP in the ER and Golgi., Lee D, Walsh JD, Mikhailenko I, Yu P, Migliorini M, Wu Y, Krueger S, Curtis JE, Harris B, Lockett S, Blacklow SC, Strickland DK, Wang YX, Mol Cell. 2006 May 5;22(3):423-30. PMID:16678114

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

Disease

[AMRP_HUMAN] Note=In complex with the alpha-2-MR or gp330, it may have some role in the pathogenesis of membrane glomerular nephritis.

Function

[AMRP_HUMAN] Interacts with LRP1/alpha-2-macroglobulin receptor and glycoprotein 330.

About this Structure

2ftu is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA.

Reference

  • Lee D, Walsh JD, Mikhailenko I, Yu P, Migliorini M, Wu Y, Krueger S, Curtis JE, Harris B, Lockett S, Blacklow SC, Strickland DK, Wang YX. RAP uses a histidine switch to regulate its interaction with LRP in the ER and Golgi. Mol Cell. 2006 May 5;22(3):423-30. PMID:16678114 doi:10.1016/j.molcel.2006.04.011

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