Structural plasticity in Ig superfamily domain 4 of ICAM-1 mediates cell surface dimerization.
Proc Natl Acad Sci U S A
; 104(39): 15358-63, 2007 Sep 25.
Article
in En
| MEDLINE
| ID: mdl-17881562
ABSTRACT
The Ig superfamily (IgSF) intercellular adhesion molecule-1 (ICAM-1) equilibrates between monomeric and dimeric forms on the cell surface, and dimerization enhances cell adhesion. A crystal structure of ICAM-1 IgSF domains (D) 3-5 revealed a unique dimerization interface in which D4s of two protomers fuse through edge beta-strands to form a single super beta-sandwich domain. Here, we describe a crystal structure at 2.7-A resolution of monomeric ICAM-1 D3-D5, stabilized by the monomer-specific Fab CA7. CA7 binds to D5 in a region that is buried in the dimeric interface and is distal from the dimerization site in D4. In monomeric ICAM-1 D3-D5, a 16-residue loop in D4 that is disordered in the dimeric structure could clearly be traced as a BC loop, a short C strand, and a CE meander with a cis-Pro followed by a solvent-exposed, flexible four-residue region. Deletions of 6 or 10 residues showed that the C-strand is essential for monomer stability, whereas a distinct six-residue deletion showed little contribution of the CE meander. Mutation of two inward-pointing Leu residues in edge beta-strand E to Lys increased monomer stability, confirming the hypothesis that inward-pointing charged side chains on edge beta-strands are an important design feature to prevent beta-supersheet formation. Overall, the studies reveal that monomer-dimer transition is associated with a surprisingly large, physiologically relevant, IgSF domain rearrangement.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Membrane
/
Intercellular Adhesion Molecule-1
/
Immunoglobulin Subunits
Limits:
Animals
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2007
Document type:
Article