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Structure paper

TitleStructural Basis for Draxin-Modulated Axon Guidance and Fasciculation by Netrin-1 through DCC.
Journal, issue, pagesNeuron, Vol. 97, Issue 6, Page 1261-11267.e4, Year 2018
Publish dateMar 21, 2018
AuthorsYing Liu / Tuhin Bhowmick / Yiqiong Liu / Xuefan Gao / Haydyn D T Mertens / Dmitri I Svergun / Junyu Xiao / Yan Zhang / Jia-Huai Wang / Rob Meijers /
PubMed AbstractAxon guidance involves the spatiotemporal interplay between guidance cues and membrane-bound cell-surface receptors, present on the growth cone of the axon. Netrin-1 is a prototypical guidance cue ...Axon guidance involves the spatiotemporal interplay between guidance cues and membrane-bound cell-surface receptors, present on the growth cone of the axon. Netrin-1 is a prototypical guidance cue that binds to deleted in colorectal cancer (DCC), and it has been proposed that the guidance cue Draxin modulates this interaction. Here, we present structural snapshots of Draxin/DCC and Draxin/Netrin-1 complexes, revealing a triangular relationship that affects Netrin-mediated haptotaxis and fasciculation. Draxin interacts with DCC through the N-terminal four immunoglobulin domains, and Netrin-1 through the EGF-3 domain, in the same region where DCC binds. Netrin-1 and DCC bind to adjacent sites on Draxin, which appears to capture Netrin-1 and tether it to the DCC receptor. We propose the conformational flexibility of the single-pass membrane receptor DCC is used to promote fasciculation and regulate axon guidance through concerted Netrin-1/Draxin binding. VIDEO ABSTRACT.
External linksNeuron / PubMed:29503192 / PubMed Central
MethodsSAS (X-ray synchrotron) / X-ray diffraction
Resolution2.493 - 3.07 Å
Structure data

SASDBZ6:
Draxin
Method: SAXS/SANS

PDB-5z5k:
Structure of the DCC-Draxin complex
Method: X-RAY DIFFRACTION / Resolution: 2.493 Å

PDB-6fkq:
THE CRYSTAL STRUCTURE OF A FRAGMENT OF NETRIN-1 IN COMPLEX WITH A FRAGMENT OF DRAXIN
Method: X-RAY DIFFRACTION / Resolution: 3.07 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-HOH:
WATER / Water

ChemComp-CA:
Unknown entry

ChemComp-SO4:
SULFATE ION / Sulfate

ChemComp-GOL:
GLYCEROL / Glycerol

Source
  • homo sapiens (human)
  • rattus norvegicus (Norway rat)
KeywordsAPOPTOSIS/INBITITOR / axon guidance / APOPTOSIS-INBITITOR complex / SIGNALING PROTEIN / AXON GUIDANCE CUE / NETRIN-1 / DRAXIN / COMMISSURAL NEURON

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