2V5S

Structural basis for Dscam isoform specificity

Summary for 2V5S

• Entry DOI: 10.2210/pdb2v5s/pdb
• Related: 2V5M 2V5R
• Descriptor: DSCAM, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: down syndrome, immunoglobulin domain, cell adhesion, membrane, developmental protein
• Biological source: DROSOPHILA MELANOGASTER (FRUIT FLY)
• Total number of polymer chains: 2
• Total formula weight: 88822.15

Authors

Meijers, R.,Puettmann-Holgado, R.,Skiniotis, G.,Liu, J.-H.,Walz, T.,Schmucker, D.,Wang, J.-H. (deposition date: 2007-07-09, release date: 2007-09-11, Last modification date: 2024-10-23)

Primary citation

Meijers, R.,Puettmann-Holgado, R.,Skiniotis, G.,Liu, J.-H.,Walz, T.,Wang, J.-H.,Schmucker, D.
Structural Basis of Dscam Isoform Specificity
Nature, 449:487-, 2007

PubMed Abstract: 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 ecto-domains, D2, D3 and D7. We report X-ray structures of the amino-terminal four immunoglobulin 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 domain 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 epitope II, confers 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.

PubMed: 17721508
DOI: 10.1038/NATURE06147

Experimental method

X-RAY DIFFRACTION (2.3 Å)