2FTU

solution structure of domain 3 of RAP


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the least restraint violations 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

RAP uses a histidine switch to regulate its interaction with LRP in the ER and Golgi.

Lee, D.Walsh, J.D.Mikhailenko, I.Yu, P.Migliorini, M.Wu, Y.Krueger, S.Curtis, J.E.Harris, B.Lockett, S.Blacklow, S.C.Strickland, D.K.Wang, Y.X.

(2006) Mol Cell 22: 423-430

  • DOI: https://doi.org/10.1016/j.molcel.2006.04.011
  • Primary Citation of Related Structures:  
    2FTU

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    Protein-Nucleic Acid Interaction Section, Structural Biophysics Laboratory, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland 21702, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Alpha-2-macroglobulin receptor-associated protein, domain 3118Homo sapiensMutation(s): 0 
Gene Names: LRPAP1
UniProt & NIH Common Fund Data Resources
Find proteins for P30533 (Homo sapiens)
Explore P30533 
Go to UniProtKB:  P30533
PHAROS:  P30533
GTEx:  ENSG00000163956 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP30533
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the least restraint violations 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-05-09
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2022-03-09
    Changes: Database references, Derived calculations
  • Version 1.4: 2024-05-29
    Changes: Data collection