3L81

Crystal structure of adaptor protein complex 4 (AP-4) mu4 subunit C-terminal domain, in complex with a sorting peptide from the amyloid precursor protein (APP)

Summary for 3L81

• Entry DOI: 10.2210/pdb3l81/pdb
• Related: 1BW8 1BXX 3G9H
• Descriptor: AP-4 complex subunit mu-1, Amyloid beta A4 protein, GLYCEROL, ... (4 entities in total)
• Functional Keywords: immunoglobulin-like beta-sandwich, coated pit, golgi apparatus, membrane, phosphoprotein, protein transport, transport, alzheimer disease, amyloid, amyloidosis, transport protein
• Biological source: Homo sapiens (human)
• Cellular location: Golgi apparatus, trans-Golgi network : O00189; Membrane; Single-pass type I membrane protein: P05067
• Total number of polymer chains: 2
• Total formula weight: 34351.99

Authors

Mardones, G.A.,Rojas, A.L.,Burgos, P.V.,Dasilva, L.L.P.,Prabhu, Y.,Bonifacino, J.S.,Hurley, J.H. (deposition date: 2009-12-29, release date: 2010-06-02, Last modification date: 2024-02-21)

Primary citation

Burgos, P.V.,Mardones, G.A.,Rojas, A.L.,daSilva, L.L.,Prabhu, Y.,Hurley, J.H.,Bonifacino, J.S.
Sorting of the Alzheimer's disease amyloid precursor protein mediated by the AP-4 complex.
Dev.Cell, 18:425-436, 2010

PubMed Abstract: Adaptor protein 4 (AP-4) is the most recently discovered and least well-characterized member of the family of heterotetrameric adaptor protein (AP) complexes that mediate sorting of transmembrane cargo in post-Golgi compartments. Herein, we report the interaction of an YKFFE sequence from the cytosolic tail of the Alzheimer's disease amyloid precursor protein (APP) with the mu4 subunit of AP-4. Biochemical and X-ray crystallographic analyses reveal that the properties of the APP sequence and the location of the binding site on mu4 are distinct from those of other signal-adaptor interactions. Disruption of the APP-AP-4 interaction decreases localization of APP to endosomes and enhances gamma-secretase-catalyzed cleavage of APP to the pathogenic amyloid-beta peptide. These findings demonstrate that APP and AP-4 engage in a distinct type of signal-adaptor interaction that mediates transport of APP from the trans-Golgi network (TGN) to endosomes, thereby reducing amyloidogenic processing of the protein.

PubMed: 20230749
DOI: 10.1016/j.devcel.2010.01.015

Experimental method

X-RAY DIFFRACTION (1.6 Å)