The mu2 subunit of the clathrin adaptor AP-2 binds to FDNPVY and YppØ sorting signals at distinct sites.
The endocytic sorting signal on the low-density lipoprotein receptor for clathrin-mediated internalization is the sequence FDNPVY in the receptor's cytosolic tail. We have used a combination of surface plasmon resonance and crosslinking with a photoactivated peptide probe to demonstrate the interaction between FDNPVY-containing peptides and the mu2 chain of purified AP-2 clathrin adaptors (the complexes responsible for plasma membrane sorting). We show that recognition of the FDNPVY signal is mediated by a binding site in the mu2-subunit that is distinct from the site for the more general YppØ sorting signal, another tyrosine-based sequence also recognized by mu2-adaptin. These results suggest the possibility that low-density lipoprotein receptor uptake may be modulated specifically and independently of other proteins in the clathrin pathway.
Boll
Werner
W
Department of Cell Biology and The Center for Blood Research, Harvard Medical School, 200 Longwood Ave, Boston, MA, 02115, USA.
Rapoport
Iris
I
Brunner
Christian
C
Modis
Yorgo
Y
Prehn
Siegfried
S
Kirchhausen
Tomas
T
D033962:Adaptor Protein Complex 2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D004705:Endocytosis; D066298:In Vitro Techniques; D007700:Kinetics; D008969:Molecular Sequence Data; D011485:Protein Binding; D021122:Protein Subunits; D011973:Receptors, LDL / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D033962:Adaptor Protein Complex 2; D021122:Protein Subunits; D011973:Receptors, LDL