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SUMMARY:Structural study of novel lipid-dependent dimerization of human GL
 TP induced by point mutation
DTSTART;VALUE=DATE-TIME:20160705T090000Z
DTEND;VALUE=DATE-TIME:20160705T100000Z
DTSTAMP;VALUE=DATE-TIME:20260307T090446Z
UID:indico-contribution-1192@indico.inp.nsk.su
DESCRIPTION:Speakers: Valeriya Samygina (FSRC "Crystallography and Photoni
 cs" RAS\, NRC "Kurchatov Institute"\, Structural Biology Unit CIC bioGUNE 
 Spain)\nProtein-protein interactions are common in cell and molecular biol
 ogy events\, and essential for cellular function. Both homodimers and hete
 rodimers are commonly involved in catalysis\, regulation and structural as
 sembly. However\, the role of dimerization in controling the action of amp
 hitropic peripheral proteins that can exist in water-soluble and lipid-bil
 ayer-bound states is not well studied. Human Glycolipid Transfer Protein (
 GLTP) carries out the important function of non-vesicular transport of gly
 cosphingolipids (GSLs) between membranes [1] but details of the all alpha-
 helical GLTP-fold mechanism of action remain unclear. Previously\, reversi
 ble lipid-dependent dimerization was discovered for holo-GLTP [2]. Structu
 ral studies using synchrotron radiation indicated a homodimer\, reproducib
 ly revealed in different crystal forms of GLTP bound with various GSLs. Th
 e homodimer is characterized by a 70-80 degree angle between wild-type mon
 omers complexed with sulfatide\, but the inter-monomer angle narrows to 63
 -66 degrees upon D48V mutation [2]. The inter-monomer contacts were found 
 to mainly involve helix6-helix6 (H6-H6)\, as well as helix2-helix2 (H2-H2)
  at their C-termini. The X-ray structure of another mutant\, K87Q\, comple
 xed with 18:1-glucosyl¬ceramide\, reveals a novel homodimer with a differ
 ent dimerization contact region that includes the mutation site\, which wa
 s not involved in the original dimerization contact region. Fluorescence s
 pectroscopy assays involving intrinsic Trp emission changes show that K87Q
 -GLTP retains the original binding capacities for such GSLs\, as sulfatide
 \, glucosylceramide and galactosylceramide. Thus\, GLTP dimer design could
  provide a way to dissect certain steps of the glycolipid transfer process
 . The influence of dimer type on steps of lipid transport by GLTP needs fu
 rther investigation.\nThis work was supported in part by Russian Foundatio
 n for Basic Research project 14-04-01671 and 15-04-07415\, NIH NIGMS GM459
 28 and NCI121493\, and CICbioGUNE research funds.\n\nReferences: \n1. Mali
 nina L\, Malakhova ML\, Kanak AT\, Lu M\, Abagyan R\, Brown RE\, Patel DJ.
  The liganding mode of glycolipid transfer protein is controlled by glycos
 phingolipid structure. \nPLoS Biol. (2006). 4:e362. \n2. Samygina VR\, Och
 oa-Lzarralde B\, Popov AN\, Cabo-Bilbao A\, Goni-de-Cerio F\, Molotkovsky 
 JG\, Patel DJ\, Brown RE\, Malinina L. Structural insights into lipid-depe
 ndent reversible dimerization of human GLTP. Acta Cryst. (2013). D69:603
 –616.\n\nhttps://indico.inp.nsk.su/event/3/contributions/1192/
LOCATION:Budker INP 2nd and 3rd floors
URL:https://indico.inp.nsk.su/event/3/contributions/1192/
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