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.
Department of Cell Biology and The Center for Blood Research, Harvard Medical School, 200 Longwood Ave, Boston, MA, 02115, USA.
Werner
W
Boll
Iris
I
Rapoport
Christian
C
Brunner
Yorgo
Y
Modis
Siegfried
S
Prehn
Tomas
T
Kirchhausen
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