Different molecular arrangements of the tetrameric annexin 2 modulate the size and dynamics of membrane aggregation.
Annexin 2, a member of the annexin family of Ca2+-dependent membrane binding proteins is found in monomeric and heterotetrameric forms and has been involved in different membrane related functions. The heterotetrameric annexin 2 is composed of a dimer of S100A10, a member of the S100 family of Ca2+ binding proteins and two annexin 2 molecules ((Anx2-S100A10)2). Different molecular models including tetramers and octamers in which S100A10 is localized in the centre of the complex with the annexin 2 molecules positioned around S100A10 had been proposed. Herein, the organization of the (Anx2-S100A10)2 complex in conditions in which membranes are able to bridge was studied. We performed Cryo-electron microscopy observations of the tetrameric annexin 2 on the membrane surface, and study the S100A10 accessibility to antibodies by flow "cytometry". We also studied the kinetics and size evolution of vesicle aggregates by dynamic light scattering. The results show that the protein is able to organize in three different arrangements depending on the presence of Ca2+ and pH and that the aggregation is faster in the presence of Ca2+ compared with the aggregation in its absence. In one arrangement the S100A10 molecule is exposed to the solvent allowing its interaction with other proteins. The presented results will serve as a molecular basis to explain some of the functions of the tetrameric annexin 2.
Illien
Françoise
F
CNRS, UMR 7203, Laboratoire des Biomolécules, Groupe N. J. Conté, Paris, France; Université Pierre et Marie Curie, CHU Saint Antoine, Paris, France; Ecole Normale Supérieure, Département de Chimie, Paris France.
Finet
Stefanie
S
Lambert
Olivier
O
Ayala-Sanmartin
Jesus
J
D017306:Annexin A2 / Q000737:chemistry*; D002118:Calcium / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011487:Protein Conformation; D055503:Protein Multimerization; D053835:Unilamellar Liposomes / Q000737:chemistry*
C472822:ANXA2 protein, human; D017306:Annexin A2; D053835:Unilamellar Liposomes; D002118:Calcium