Biomedical Engineering Reference
In-Depth Information
of anti-parallel β strands stabilized by a disuli de bridge, producing a compact
structure relatively insensitive to proteolytic cleavage. h e V subtype contains the
antigen-binding properties and consists of nine β strands, while the C subtype
mediates ef ector functions and contains seven β strands (Barclay 2003).
As these domains were i rst described in immunoglobulins, it was thought they
had developed to allow antibody recognition and were specii c to the immune
system. However, as increasing numbers of proteins were found with similar
domains, it became clear that this arrangement is ancient in evolutionary terms
and mediates a wide array of interactions outside the immune system (Barclay
2003). h ese sequences are called IgSF domains or Ig-like domains, distinguishing
them from the domains of immunoglobulins (Barclay 2003).
h e IgSF domains are classii ed as V, C1, C2 or I (intermediate), according to
sequence patterns and length. C1 corresponds to the C domain of immunoglobulins,
whereas C2 is a variant found in most other IgSF proteins. h e I domain is
structurally similar to the V domain, but also contains features characteristic of C
domains (Harpaz and Chothia 1994). IgSF domains contain relatively few highly
conserved residues, and recognizing these domains can be dii cult. Characteristic
features of IgSF domains include alternating hydrophobic residues in the β strands
and the conserved cysteine residues that form disuli de bonds between the two
β-sheets.
Structure of IgSF Cell Adhesion Molecules
Most IgSF members are type I membrane proteins, consisting of an amino
N-terminal extracellular region, a single transmembrane domain and a carboxyl
C-terminal cytoplasmic domain (Barclay 2003). h e extracellular domains of IgSF
CAMs contain a number of Ig-like domains and many also contain one or more
in the ECM protein i bronectin and consists of overlapping β-sheets containing
seven anti-parallel β-strands. h is topology is similar to the immunoglobulin C
domain, although the FNIII domain is not stabilized by a disuli de bridge (Harpaz
and Chothia 1994).
In CAMs with multiple Ig-like domains, one or more V-type domain(s) are
usually located closest to the N-terminus, followed by one or more C2-type
domain(s). When present, the FNIII domains are adjacent to the membrane
(Aricescu and Jones 2007). h e transmembrane domains of IgSF CAMs are small,
while the intracellular domains vary in length, with many containing signaling
motifs and/or regions that interact with cytoskeletal or adaptor elements (Barclay
2003). h us, interactions of IgSF CAMs at the cell surface can lead to signaling
within the cell (outside-in signaling) and inside-out signaling.
