2oz4
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Structural Plasticity in IgSF Domain 4 of ICAM-1 Mediates Cell Surface Dimerization
OverviewOverview
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.
DiseaseDisease
Known disease associated with this structure: Malaria, cerebral, susceptibility to OMIM:[147840]
About this StructureAbout this Structure
2OZ4 is a Single protein structure of sequence from Homo sapiens and Mus musculus with NAG, SO4, ZN and TRS as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Structural plasticity in Ig superfamily domain 4 of ICAM-1 mediates cell surface dimerization., Chen X, Kim TD, Carman CV, Mi LZ, Song G, Springer TA, Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15358-63. Epub 2007 Sep 19. PMID:17881562
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