This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Drosophila 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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR011823-14
Application #
7957683
Study Section
Special Emphasis Panel (ZRG1-CB-H (40))
Project Start
2009-09-01
Project End
2010-08-31
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
14
Fiscal Year
2009
Total Cost
$1,392
Indirect Cost
Name
University of Washington
Department
Biochemistry
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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