Differential lipid specificities of the repeated domains of annexin IV.
The roles of the four domains of annexin IV in binding to phospholipids and glycolipids were assessed by analyzing the binding of a group of mutant annexins IV in which one or more of the four domains was inactivated by replacing a critical amino residue(s) (Asp or Glu) with the neutral residue Ala. The data reveal that individual annexin domains may have characteristic affinities for different lipids. In particular, inactivation of the fourth domain inhibits the binding to phosphatidylserine (PS) and phosphatidylinositol (PI) but not to phosphatidylglycerol (PG), suggesting that this domain specifically can accommodate the larger head groups of PS and PI whereas the other three domains may form more restricted binding pockets. In order to block binding to PG, domain 1, or both domains 2 and 3 must be inactivated in addition to domain 4, suggesting that all four domains may be able to accommodate the headgroup of PG to some extent. Binding to acidic glycolipids (sulfatides) was also sensitive to inactivation of domain 4. However, in the case of sulfatides the nature of the binding reaction is fundamentally different compared with the binding to phospholipids since the interaction with sulfatides was highly sensitive to an increase in ionic strength. The binding to sulfatides may depend therefore on charge-charge interactions whereas the binding to phospholipid may involve a more specific interaction between the lipid headgroup and the protein surface, and/or interaction of the protein with the hydrophobic portion of a lipid bilayer.
Sohma
H
H
Department of Biochemistry, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-ku, Sapporo 060-8556, Japan. sohma@sapmed.ac,jp
Creutz
C E
CE
Gasa
S
S
Ohkawa
H
H
Akino
T
T
Kuroki
Y
Y
D000409:Alanine / Q000737:chemistry; D017314:Annexin A4 / Q000737:chemistry / Q000235:genetics*; D001224:Aspartic Acid / Q000737:chemistry; D001665:Binding Sites; D002118:Calcium; D018698:Glutamic Acid / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D008563:Membrane Lipids / Q000737:chemistry*; D009154:Mutation; D010743:Phospholipids / Q000737:chemistry*; D012965:Sodium Chloride
D017314:Annexin A4; D008081:Liposomes; D008563:Membrane Lipids; D010743:Phospholipids; D001224:Aspartic Acid; D018698:Glutamic Acid; D012965:Sodium Chloride; D000409:Alanine; D002118:Calcium