3dmk
Crystal structure of Down Syndrome Cell Adhesion Molecule (DSCAM) isoform 1.30.30, N-terminal eight Ig domainsCrystal structure of Down Syndrome Cell Adhesion Molecule (DSCAM) isoform 1.30.30, N-terminal eight Ig domains
Structural highlights
FunctionDSCA1_DROME Cell surface receptor involved in guidance and targeting of growing nerve axons (PubMed:10892653). Required during Bolwig's organ differentiation for accurate and efficient targeting of photoreceptor neuron axons to their synaptic targets in the brain via the P2 intermediate target neuron (PubMed:10892653). Involved in isoneural self-avoidance during dendrite arborization but not in heteroneural recognition and repulsion during tiling by related neurons of the same class (PubMed:17482551). Involved in regulating axon bifurcation and divergent extension in the developing mushroom body (PubMed:11856530, PubMed:15339648). Essential for axon arborisation in ellipsoid body (PubMed:11856530, PubMed:15339648). Exhibits an extraordinary level of molecular diversity resulting from alternative splicing (PubMed:10892653). Isoforms differing in their ectodomain makeup show a high degree of functional redundancy while isoforms with different transmembrane domains are involved in different neuronal morphogenetic processes and are differentially targeted to dendrites or axons (PubMed:15339648). The vast majority of isoforms exhibit strong isoform-specific homophilic binding (PubMed:15339666, PubMed:17889655). Individual cells express a distinct randomly generated repertoire of isoforms (PubMed:14758360). Cell surfaces bearing identical repertoires of Dscam1 isoforms, such as those from the same cell, trigger recognition and avoidance (PubMed:17482551). A subset of isoforms is expressed in fat body cells and hemocytes, cells that are part of the insect immune response, and these isoforms are secreted into the hemolymph (PubMed:16109846). The secreted form comprising the ectodomain can bind to bacteria, such as Escherichia coli, and may act as an opsonin enhancing their phagocytosis by hemocytes (PubMed:16109846).[1] [2] [3] [4] [5] [6] [7] [8] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedDrosophila Dscam encodes a vast family of immunoglobulin (Ig)-containing proteins that exhibit isoform-specific homophilic binding. This diversity is essential for cell recognition events required for wiring the brain. Each isoform binds to itself but rarely to other isoforms. Specificity is determined by "matching" of three variable Ig domains within an approximately 220 kD ectodomain. Here, we present the structure of the homophilic binding region of Dscam, comprising the eight N-terminal Ig domains (Dscam(1-8)). Dscam(1-8) forms a symmetric homodimer of S-shaped molecules. This conformation, comprising two reverse turns, allows each pair of the three variable domains to "match" in an antiparallel fashion. Structural, genetic, and biochemical studies demonstrate that, in addition to variable domain "matching," intramolecular interactions between constant domains promote homophilic binding. These studies provide insight into how "matching" at all three pairs of variable domains in Dscam mediates isoform-specific recognition. A double S shape provides the structural basis for the extraordinary binding specificity of Dscam isoforms.,Sawaya MR, Wojtowicz WM, Andre I, Qian B, Wu W, Baker D, Eisenberg D, Zipursky SL Cell. 2008 Sep 19;134(6):1007-18. PMID:18805093[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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