Recognition of dileucine-based sorting signals from HIV-1 Nef and LIMP-II by the AP-1 gamma-sigma1 and AP-3 delta-sigma3 hemicomplexes.
The sorting of transmembrane proteins to endosomes and lysosomes is mediated by signals present in the cytosolic tails of the proteins. A subset of these signals conform to the [DE]XXXL[LI] consensus motif and mediate sorting via interactions with heterotetrameric adaptor protein (AP) complexes. However, the identity of the AP subunits that recognize these signals remains controversial. We have used a yeast three-hybrid assay to demonstrate that [DE]XXXL[LI]-type signals from the human immunodeficiency virus negative factor protein and the lysosomal integral membrane protein II interact with combinations of the gamma and sigma1 subunits of AP-1 and the delta and sigma3 subunits of AP-3, but not the analogous combinations of AP-2 and AP-4 subunits. The sequence requirements for these interactions are similar to those for binding to the whole AP complexes in vitro and for function of the signals in vivo. These observations reveal a novel mode of recognition of sorting signals involving the gamma/delta and sigma subunits of AP-1 and AP-3.
Janvier
Katy
K
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Kato
Yukio
Y
Boehm
Markus
M
Rose
Jeremy R
JR
Martina
José A
JA
Kim
Bong-Yoon
BY
Venkatesan
Sundararajan
S
Bonifacino
Juan S
JS
D033963:Adaptor Protein Complex 3; D018955:CD36 Antigens / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000378:metabolism; D015693:Gene Products, nef / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000378:metabolism; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D051116:Receptors, Scavenger; D012441:Saccharomyces cerevisiae; D012795:Sialoglycoproteins; D015398:Signal Transduction / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D033963:Adaptor Protein Complex 3; D018955:CD36 Antigens; D004268:DNA-Binding Proteins; D015693:Gene Products, nef; D051907:Lysosomal Membrane Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D021122:Protein Subunits; D051116:Receptors, Scavenger; C074299:SCARB2 protein, human; D012795:Sialoglycoproteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors