2WFH

The Human Slit 2 Dimerization Domain D4

Summary for 2WFH

• Entry DOI: 10.2210/pdb2wfh/pdb
• Related: 2V70 2V9S 2V9T
• Descriptor: SLIT HOMOLOG 2 PROTEIN C-PRODUCT, SULFATE ION (3 entities in total)
• Functional Keywords: developmental protein, neurogenesis, splicing, glycoprotein, leucine-rich repeat, disulfide bond, differentiation, egf-like domain, id14-eh4, roundabout, chemotaxis, nerve cell, midline, heparan, heparin, secreted, guidance, d4, xds, lrr, slit, axon, neuron, phaser, sulfate
• Biological source: HOMO SAPIENS
• Total number of polymer chains: 2
• Total formula weight: 43017.46

Authors

Seiradake, E.,von Philipsborn, A.C.,Henry, M.,Fritz, M.,Lortat-Jacob, H.,Jamin, M.,Hemrika, W.,Bastmeyer, M.,Cusack, S.,McCarthy, A.A. (deposition date: 2009-04-06, release date: 2009-04-21, Last modification date: 2023-12-13)

Primary citation

Seiradake, E.,von Philipsborn, A.C.,Henry, M.,Fritz, M.,Lortat-Jacob, H.,Jamin, M.,Hemrika, W.,Bastmeyer, M.,Cusack, S.,McCarthy, A.A.
Structure and functional relevance of the Slit2 homodimerization domain.
EMBO Rep., 10:736-741, 2009

PubMed Abstract: Slit proteins are secreted ligands that interact with the Roundabout (Robo) receptors to provide important guidance cues in neuronal and vascular development. Slit-Robo signalling is mediated by an interaction between the second Slit domain and the first Robo domain, as well as being dependent on heparan sulphate. In an effort to understand the role of the other Slit domains in signalling, we determined the crystal structure of the fourth Slit2 domain (D4) and examined the effects of various Slit2 constructs on chick retinal ganglion cell axons. Slit2 D4 forms a homodimer using the conserved residues on its concave face, and can also bind to heparan sulphate. We observed that Slit2 D4 frequently results in growth cones with collapsed lamellipodia and that this effect can be inhibited by exogenously added heparan sulphate. Our results show that Slit2 D4-heparan sulphate binding contributes to a Slit-Robo signalling mechanism more intricate than previously thought.

PubMed: 19498462
DOI: 10.1038/embor.2009.95

Experimental method

X-RAY DIFFRACTION (1.8 Å)