2OZ4

Structural Plasticity in IgSF Domain 4 of ICAM-1 Mediates Cell Surface Dimerization

Summary for 2OZ4

• Entry DOI: 10.2210/pdb2oz4/pdb
• Descriptor: Intercellular adhesion molecule 1, FAB FRAGMENT LIGHT CHAIN, FAB FRAGMENT, HEAVY CHAIN, ... (9 entities in total)
• Functional Keywords: igsf domain, structural plasticity, cell-surface dimerization, cell adhesion
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 76425.73

Authors

Chen, X.,Kim, T.D.,Carman, C.V.,Mi, L.,Song, G.,Springer, T.A. (deposition date: 2007-02-23, release date: 2007-10-16, Last modification date: 2024-11-13)

Primary citation

Chen, X.,Kim, T.D.,Carman, C.V.,Mi, L.Z.,Song, G.,Springer, T.A.
Structural plasticity in Ig superfamily domain 4 of ICAM-1 mediates cell surface dimerization.
Proc.Natl.Acad.Sci.Usa, 104:15358-15363, 2007

PubMed 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.

PubMed: 17881562
DOI: 10.1073/pnas.0707406104

Experimental method

X-RAY DIFFRACTION (2.7 Å)