2oz4
From Proteopedia
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | The Ig superfamily (IgSF) intercellular adhesion molecule-1 (ICAM-1) | + | 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. |
| + | |||
| + | ==Disease== | ||
| + | Known disease associated with this structure: Malaria, cerebral, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147840 147840]] | ||
==About this Structure== | ==About this Structure== | ||
| Line 14: | Line 17: | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Carman, C | + | [[Category: Carman, C V.]] |
[[Category: Chen, X.]] | [[Category: Chen, X.]] | ||
| - | [[Category: Kim, T | + | [[Category: Kim, T D.]] |
[[Category: Mi, L.]] | [[Category: Mi, L.]] | ||
[[Category: Song, G.]] | [[Category: Song, G.]] | ||
| - | [[Category: Springer, T | + | [[Category: Springer, T A.]] |
[[Category: NAG]] | [[Category: NAG]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
| Line 29: | Line 32: | ||
[[Category: structural plasticity]] | [[Category: structural plasticity]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:24:07 2008'' |
Revision as of 16:24, 21 February 2008
|
Structural Plasticity in IgSF Domain 4 of ICAM-1 Mediates Cell Surface Dimerization
Contents |
Overview
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.
Disease
Known disease associated with this structure: Malaria, cerebral, susceptibility to OMIM:[147840]
About this Structure
2OZ4 is a Single protein structure of sequence from Homo sapiens and Mus musculus with , , and as ligands. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 18:24:07 2008
Categories: Homo sapiens | Mus musculus | Single protein | Carman, C V. | Chen, X. | Kim, T D. | Mi, L. | Song, G. | Springer, T A. | NAG | SO4 | TRS | ZN | Cell adhesion | Cell-surface dimerization | Igsf domain | Structural plasticity
