Ak. Hinderliter et al., Membrane domain formation by calcium-dependent, lipid-binding proteins: insights from the C2 motif, BBA-MOL CEL, 1448(2), 1998, pp. 227-235
Citations number
46
Categorie Soggetti
Cell & Developmental Biology
Journal title
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
We propose a novel role in cellular function for some membrane-binding prot
eins and, specifically, the C2 motif. The C2 motif binds phospholipid in a
manner that is modulated by Ca2+ and is thought to confer membrane-binding
ability on a wide variety of proteins, primarily proteins involved in signa
l transduction and membrane trafficking events. We hypothesize that in the
absence of Ca2+ the C2 motif couples the free energy of binding to a bilaye
r membrane comprised of zwitterionic and negatively charged lipids to the f
ormation of a domain enriched in the negative lipids. This in turn leads to
the dynamic clustering of bound homologous or heterologous proteins incorp
orating the C2 motif, or other acidic lipid-binding motifs. In the presence
of Ca2+, the protein clusters may be further stabilized. In support of thi
s hypothesis we present evidence for membrane domain formation by the first
C2 domain of synaptotagmin in the absence of Ca2+. Fluid state phospholipi
d mixtures incorporating a pyrene-labeled phospholipid probe exhibited a ch
ange in pyrene excimer/monomer fluorescence ratio consistent with domain fo
rmation upon binding the C2 domain. In addition, we present the results of
simulations of the interaction of the C2 domain with the membrane that indi
cate that protein clusters and lipid domains form in concert. (C) 1998 Else
vier Science B.V. All rights reserved.