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SUMMARY:Membrane activation of the adaptor complex AP2 in clathrin-mediate
 d endocytosis - Dr. Phil Evans MRC Laboratory of Molecular Biology
DTSTART:20101006T093000Z
DTEND:20101006T103000Z
UID:TALK27020@talks.cam.ac.uk
CONTACT:benedetta bolognesi
DESCRIPTION:Membrane proteins are packaged for transport between the diffe
 rent membrane compartments of eukaryotic cells into small vesicles formed 
 by an elaborate system of cytoplasmic proteins. Selection of cargo for ves
 icle formation at the plasma membrane (endocytosis) is generally mediated 
 directly or indirectly by the heterotetrameric clathrin adaptor complex AP
 2\, which binds short sequence recognition motifs of two types\, YxxΦ (ty
 rosine-based motif\, where Φ is a hydrophobic residue) and [DE]xxxLL (aci
 dic dileucine motif). The structure of the 200kDa AP2 “core” crystalli
 sed in the absence of peptides showed a closed conformation\, with binding
  sites for both types of motifs blocked\, and indeed AP2 in solution does 
 not bind motif peptides. AP2 is activated by binding to negatively charged
  membranes containing phosphatidylinositol-(4\,5)-bisphosphate. We were ab
 le to trap the activated “open”  conformation in crystals grown with a
  YxxΦ peptide\, and this structure shows a large conformational change co
 mpared to the closed “locked” conformation\, with the YxxΦ-binding do
 main moving out of the “bowl” formed by the other subunits. This place
 s both peptide sites on the positively-charged face of the complex\, allow
 ing simultaneous interaction with cargo motifs and the membrane. Thus AP2 
 functions as a plasma membrane-activated switch for endocytic cargo recogn
 ition.
LOCATION:Unilever Lecture Theatre\,  Department of Chemistry
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