Phospholipid species act as modulators in p97/p47-mediated fusion of Golgi membranes

Biochemistry. 2002 Aug 6;41(31):9813-23. doi: 10.1021/bi0259195.

Abstract

The ATPase p97 in complex with p47 participates in Golgi cisternae rebuilding after mitosis. In a Golgi-liposome assay, the complex triggered a phosphatidylethanolamine (PE)-promoted fusion. Here we show for the first time that fusion between mitotic Golgi membranes induced by adding cytosol or purified p97/p47 is modulated by PE present in Golgi membranes. Using model membranes, we demonstrate a PE-dependent recruitment of p97/p47 to membranes, causing dramatic conformational rearrangements and favoring protein-lipid interactions. Previously buried hydrophobic sites become exposed in a controlled manner, which leads to the penetration of (a) domain(s) of the complex into lipid bilayers, facilitated by a PE-dependent increase in headgroup spacing. In contrast, when facing phosphatidylcholine (PC) the complex clusters extensively. This implies that in the presence of PC protein-protein interactions rather than fusion-promoting protein-lipid interactions occur. Importantly, PE-mediated changes in secondary and tertiary structures are exclusively observed when p97 is complexed with p47, which is a prerequisite for membrane fusion. We therefore propose that at physiological conditions PE-induced conformational changes in p97/p47 are relevant in triggering this activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Animals
  • Golgi Apparatus / metabolism*
  • Membrane Fusion*
  • Nuclear Proteins / metabolism*
  • Phospholipids / metabolism*
  • Rats
  • Spectrometry, Fluorescence
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Nuclear Proteins
  • Phospholipids
  • Adenosine Triphosphatases
  • p97 ATPase