RGD Reference Report - Structural basis of the cytoplasmic tail of adhesion molecule CD43 and its binding to ERM proteins. - Rat Genome Database

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Structural basis of the cytoplasmic tail of adhesion molecule CD43 and its binding to ERM proteins.

Authors: Takai, Y  Kitano, K  Terawaki, S  Maesaki, R  Hakoshima, T 
Citation: Takai Y, etal., J Mol Biol. 2008 Sep 5;381(3):634-44. Epub 2008 Jun 7.
RGD ID: 2303981
Pubmed: PMID:18614175   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jmb.2008.05.085   (Journal Full-text)

CD43/leukosialin/sialophorin is the major adhesion molecule in most hematopoietic cells and belongs to the sialomucin superfamily. In leukocyte emigration and activation, the exclusion of CD43 from the immunological synapse is an essential step. While the exclusion requires binding of the cytoplasmic region to ERM (ezrin/radixin/moesin) proteins, the detailed specific nature of the interaction between CD43 and ERM proteins is obscure. We have characterized the conformational properties of the CD43 cytoplasmic region, consisting of 124 amino acid residues, by hydrodynamic and spectroscopic measurements. Sedimentation equilibrium and velocity studies of ultracentrifugation revealed that the CD43 cytoplasmic peptide exists in a monomeric and extended form in solution. The crystal structure of the complex between the radixin FERM (4.1 and ERM) domain and the CD43 juxtamembrane region peptide reveals that the nonpolar region of the peptide binds subdomain C of the FERM domain. CD43 lacks the Motif-1 sequence for FERM binding found in the FERM-intercellular adhesion molecule-2 complex but possesses two conserved leucine residues that dock into the hydrophobic pocket of subdomain C without forming a 3(10)-helix. The FERM-binding site on CD43 is overlapped with the functional nuclear localization signal sequence. Our structure suggests that regulation of ERM binding may be coupled with regulated intramembrane proteolysis of CD43 followed by the nuclear transfer of the cytoplasmic peptide.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SpnRatprotein domain specific binding  IPIRdx (Mus musculus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Spn  (sialophorin)


Additional Information