2V5R

Structural basis for Dscam isoform specificity

2V5R の概要

• エントリーDOI: 10.2210/pdb2v5r/pdb
• 関連するPDBエントリー: 2V5M 2V5S
• 分子名称: DSCAM, 2-acetamido-2-deoxy-beta-D-glucopyranose, GLYCEROL (3 entities in total)
• 機能のキーワード: down syndrome cell adhesion molecule dscam neurobiology spl immunoglobulin domain, membrane, cell adhesion, developmental protein
• 由来する生物種: DROSOPHILA MELANOGASTER (FRUIT FLY)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 88905.87

構造登録者

Meijers, R.,Puettmann-Holgado, R.,Skiniotis, G.,Liu, J.-H.,Walz, T.,Schmucker, D.,Wang, J.-H. (登録日: 2007-07-09, 公開日: 2007-09-11, 最終更新日: 2024-11-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3 Å)