NORTHWESTERN UNIVERSITY FEINBERG SCHOOL OF MEDICINE
DAVEE DEPARTMENT OF NEUROLOGY
SEMINAR
 
“One Stone for Two Birds: Dscam Serves for both Neuronal and Immune Systems”
 
Friday, March 14, 2008
2:00-3:00 pm
Physiology Conference Room, Ward 5-230

Jia-huai Wang, PhD
Associate Professor of Pediatrics and Biological Chemistry and Molecular Pharmacology
 
Harvard Medical School
Boston, MA
 
The Dscam gene gives rise to thousands of diverse cell surface receptors thought to provide homophilic and heterophilic recognition specificity for neuronal wiring and immune responses.  Mutually exclusive splicing allows for the generation of sequence variability in three immunoglobulin (Ig) ecto-domains (D2, D3, D7).  We determined x-ray structures of the N-terminal four Ig domains (D1-D4) of two distinct Dscam isoforms.  The structures reveal a horseshoe configuration, with variable residues of D2 and D3 constituting two independent surface-epitopes on either side of the receptor.  Both isoforms engage in homo-dimerization coupling variable domains D2 with D2 and D3 with D3.  These interactions involve symmetric, antiparallel-pairing of identical peptide segments from epitope I that are unique to each isoform. Structure-guided mutagenesis and swapping of peptide segments confirm that epitope I but not II confer homophilic binding specificity of full-length Dscam receptors.  Phylogenetic analysis shows strong selection of matching peptide sequences only for epitope I.  We propose that peptide-complementarity of variable residues in epitope I of Dscam is essential for homophilic binding specificity.
 
 
REFRESHMENTS WILL BE PROVIDED
 
Hosted by Dr. Jane Wu