PDBsum entry 2oz4

Cell adhesion

PDB id: 2oz4

Contents

Protein chains

265 a.a. *

214 a.a. *

208 a.a. *

Ligands

NAG-FUC

NAG ×2

SO4 ×2

TRS ×2

Metals

_ZN ×2

Waters ×276

* Residue conservation analysis

PDB id:

2oz4

Name:

Cell adhesion

Title:

Structural plasticity in igsf domain 4 of icam-1 mediates cell surface dimerization

Structure:

Intercellular adhesion molecule 1. Chain: a. Engineered: yes. Fab fragment light chain. Chain: l. Fab fragment, heavy chain. Chain: h

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: icam1. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Mus musculus. House mouse. Organism_taxid: 10090.

Resolution:

2.70Å R-factor: 0.209 R-free: 0.253

Authors:

X.Chen,T.D.Kim,C.V.Carman,L.Mi,G.Song,T.A.Springer

Key ref:

X.Chen et al. (2007). Structural plasticity in Ig superfamily domain 4 of ICAM-1 mediates cell surface dimerization. Proc Natl Acad Sci U S A, 104, 15358-15363. PubMed id: 17881562 DOI: 10.1073/pnas.0707406104

Date:

23-Feb-07 Release date: 16-Oct-07

Protein chain

P05362  (ICAM1_HUMAN) -  Intercellular adhesion molecule 1 from Homo sapiens

Seq: 532 a.a.

Struc: 265 a.a.*

Protein chain

No UniProt id for this chain

Struc: 214 a.a.

Protein chain

P01757  (HVM13_MOUSE) -  Ig heavy chain V region J558 from Mus musculus

Seq: 117 a.a.

Struc: 208 a.a.*

* PDB and UniProt seqs differ at 25 residue positions (black crosses)

DOI no: 10.1073/pnas.0707406104

Proc Natl Acad Sci U S A 104:15358-15363 (2007)

PubMed id: 17881562

Structural plasticity in Ig superfamily domain 4 of ICAM-1 mediates cell surface dimerization.

X.Chen, T.D.Kim, C.V.Carman, L.Z.Mi, G.Song, T.A.Springer.

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.

Selected figure(s)

Figure 3.
Fig. 3. Structural properties of D4. (A) Backbone C^ trace of D4 colored in rainbow from highest (red) to lowest (blue) B factor. Atoms of cis-Pro-319 and atoms C and O of Val-318 are represented with sticks, and the hydrogen bond in the turn between the C-strand and CE meander is dashed. The disulfide bond is shown in yellow. (B) Comparison of the CE edges of D2 (magenta) and monomeric D4 (cyan) of ICAM-1. Superposition is on -strands B, C, E, and F and the region containing -strands A, A', and G is omitted for clarity.

Figure 4.
Fig. 4. The CA7 Fab binding site in D5. CA7 Fab is shown as a surface representation colored in wheat (heavy chain) and light blue (light chain) bound to monomeric D5 shown as a magenta ribbon, with indicated side chains in the AA loop at the center of the epitope as black sticks. Dimeric D4 and D5 are shown as ribbons with a cyan monomer and a yellow monomer superimposed on monomeric D5. The inward-pointing Leu residues of -strand E of the cyan monomer are shown as blue sticks.

Figures were selected by an automated process.