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SUMMARY:Short Talk 6\, Mikael B. L. Winkler - STRUCTURAL INSIGHT INTO EUKA
 RYOTIC STEROL TRANSPORT THROUGH NIEMANN-PICK TYPE C PROTEINS
DTSTART;VALUE=DATE-TIME:20191010T091000Z
DTEND;VALUE=DATE-TIME:20191010T093000Z
DTSTAMP;VALUE=DATE-TIME:20260526T034224Z
UID:indico-contribution-763@lindico453.srv.lu.se
DESCRIPTION:Speakers: Mikael Winkler (Aarhus University)\nNiemann-Pick typ
 e C (NPC) proteins are essential for sterol homeostasis\, believed to driv
 e sterol integration into the vacuolar/lysosomal membrane before redistrib
 ution to other cellular membranes. Using a combination of crystallography\
 , cryo-electronmicroscopy\, biochemical and in vivo studies on the Sacchar
 omyces cerevisiae NPC system\, NCR1/NPC2\, we recently generated a framewo
 rk for sterol membrane integration (Winkler et al.\, (2019)). Sterols are 
 transferred between hydrophobic pockets of vacuolar NPC2 and membrane-prot
 ein NCR1. NCR1 has its N terminal domain (NTD) positioned to deliver a ste
 rol to a tunnel connecting NTD to the luminal membrane leaflet 50 Å away.
  A sterol is caught inside this tunnel during transport\, and a proton-rel
 ay network of charged residues in the transmembrane region is linked to th
 is tunnel supporting a proton-driven transport mechanism. We propose a mod
 el for sterol integration which clarifies the role of NPC proteins in this
  essential eukaryotic pathway and which rationalizes mutations in patients
  with Niemann-Pick disease Type C that I will present at the talk.\n\nWink
 ler et al\, Structural insight into eukaryotic sterol transport through Ni
 emann-Pick Type C proteins\, Cell (accepted\, 2019)\n\nhttps://lindico453.
 srv.lu.se/event/125/contributions/763/
LOCATION:Kulturen Auditorium
URL:https://lindico453.srv.lu.se/event/125/contributions/763/
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