Family 1.A.31 - The Annexin Family
Family ID: 53371
The annexins are a structurally conserved family of proteins characterized
by reversible Ca2+-dependent intracellular membrane binding. Membrane
association is critical for their proposed functions which include
vesicle trafficking, membrane fusion and ion channel formation.
High-resolution crystal structures of the soluble forms of several
annexins are available. These include hydra annexin XII and human
annexin V. A low resolution structure is available for the membrane-bound
Annexin 5 trimer (Oling et al, 2000). These proteins bind to surfaces
of phosphatidylserine-containing phospholipid bilayers either
in the presence of Ca2+ or under conditions of low pH (pH 5-6).
Then they undergo major conformational changes involving three
states: (1) soluble state (monomer) --> (2) peripheral membrane-associated
state (trimer) --> (3) integral transmembrane channel state
(hexamer). This last state requires major conformational changes
with the formation of a putative polytopic, amphipathic channel.
Ca2+ induces dimer, trimer and hexamer formation as well as phospholipid
association. A helix-loop-helix structure in the soluble form
is believed to be converted into one of the continuous transmembrane
a-helices.
All annexins
display a conserved core domain consisting of four homologous
repeats, each of about 70 residues. Two of these repeat units
may comprise a single Ca2+/phospholipid binding site. The ion
channel properties of the integral membrane forms of annexins
have been amply documented. Annexins are also called Lipocortins,
Synexins, Endonexins and Calpactins. Most are 310-350 residues
long.
Annexins comprise
a large family with more than 100 sequenced proteins from over
45 species. They are found throughout the eukaryotic kingdoms.
They have been subdivided into three groups: (1) tetradcore with
short amino termini; (2) tetradcore with long amino termini; (3)
octadcore with short amino termini. The core is a 34kDa C-terminal
domain of 4 repeats except for annexin VI which has 8 repeats.
Each repeat is 70aas with an "endonexin fold" with its
identifying GXGTDE sequence. Each repeat forms a compact a-helical
domain consisting of 5 a -helicies wound in a right-handed superhelix.
The four domains are arranged in a flat cylindrical array with
the hydrophilic channel in the center of the molecule. Ca2+ is
preferred over other divalent cations, but both cations and anions
can be transported
