7ol2

Crystal structure of mouse contactin 1 immunoglobulin domainsCrystal structure of mouse contactin 1 immunoglobulin domains

Structural highlights

7ol2 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.89Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CNTN1_MOUSE Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between axons and myelinating glial cells via its association with CNTNAP1. Participates in oligodendrocytes generation by acting as a ligand of NOTCH1. Its association with NOTCH1 promotes NOTCH1 activation through the released notch intracellular domain (NICD) and subsequent translocation to the nucleus. Interaction with TNR induces a repulsion of neurons and an inhibition of neurite outgrowth.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Cell-surface expressed contactin 1 and neurofascin 155 control wiring of the nervous system and interact across cells to form and maintain paranodal myelin-axon junctions. The molecular mechanism of contactin 1 - neurofascin 155 adhesion complex formation is unresolved. Crystallographic structures of complexed and individual contactin 1 and neurofascin 155 binding regions presented here, provide a rich picture of how competing and complementary interfaces, post-translational glycosylation, splice differences and structural plasticity enable formation of diverse adhesion sites. Structural, biophysical, and cell-clustering analysis reveal how conserved Ig1-2 interfaces form competing heterophilic contactin 1 - neurofascin 155 and homophilic neurofascin 155 complexes whereas contactin 1 forms low-affinity clusters through interfaces on Ig3-6. The structures explain how the heterophilic Ig1-Ig4 horseshoe's in the contactin 1 - neurofascin 155 complex define the 7.4 nm paranodal spacing and how the remaining six domains enable bridging of distinct intercellular distances.

Structural insights into the contactin 1 - neurofascin 155 adhesion complex.,Chataigner LMP, Gogou C, den Boer MA, Frias CP, Thies-Weesie DME, Granneman JCM, Heck AJR, Meijer DH, Janssen BJC Nat Commun. 2022 Nov 3;13(1):6607. doi: 10.1038/s41467-022-34302-9. PMID:36329006^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Boyle ME, Berglund EO, Murai KK, Weber L, Peles E, Ranscht B. Contactin orchestrates assembly of the septate-like junctions at the paranode in myelinated peripheral nerve. Neuron. 2001 May;30(2):385-97. PMID:11395001
↑ Hu QD, Ang BT, Karsak M, Hu WP, Cui XY, Duka T, Takeda Y, Chia W, Sankar N, Ng YK, Ling EA, Maciag T, Small D, Trifonova R, Kopan R, Okano H, Nakafuku M, Chiba S, Hirai H, Aster JC, Schachner M, Pallen CJ, Watanabe K, Xiao ZC. F3/contactin acts as a functional ligand for Notch during oligodendrocyte maturation. Cell. 2003 Oct 17;115(2):163-75. doi: 10.1016/s0092-8674(03)00810-9. PMID:14567914 doi:http://dx.doi.org/10.1016/s0092-8674(03)00810-9
↑ Pesheva P, Gennarini G, Goridis C, Schachner M. The F3/11 cell adhesion molecule mediates the repulsion of neurons by the extracellular matrix glycoprotein J1-160/180. Neuron. 1993 Jan;10(1):69-82. doi: 10.1016/0896-6273(93)90243-k. PMID:7678967 doi:http://dx.doi.org/10.1016/0896-6273(93)90243-k
↑ Chataigner LMP, Gogou C, den Boer MA, Frias CP, Thies-Weesie DME, Granneman JCM, Heck AJR, Meijer DH, Janssen BJC. Structural insights into the contactin 1 - neurofascin 155 adhesion complex. Nat Commun. 2022 Nov 3;13(1):6607. doi: 10.1038/s41467-022-34302-9. PMID:36329006 doi:http://dx.doi.org/10.1038/s41467-022-34302-9

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OCA

[1] Boyle ME, Berglund EO, Murai KK, Weber L, Peles E, Ranscht B. Contactin orchestrates assembly of the septate-like junctions at the paranode in myelinated peripheral nerve. Neuron. 2001 May;30(2):385-97. PMID:11395001

[2] Hu QD, Ang BT, Karsak M, Hu WP, Cui XY, Duka T, Takeda Y, Chia W, Sankar N, Ng YK, Ling EA, Maciag T, Small D, Trifonova R, Kopan R, Okano H, Nakafuku M, Chiba S, Hirai H, Aster JC, Schachner M, Pallen CJ, Watanabe K, Xiao ZC. F3/contactin acts as a functional ligand for Notch during oligodendrocyte maturation. Cell. 2003 Oct 17;115(2):163-75. doi: 10.1016/s0092-8674(03)00810-9. PMID:14567914 doi:http://dx.doi.org/10.1016/s0092-8674(03)00810-9

[3] Pesheva P, Gennarini G, Goridis C, Schachner M. The F3/11 cell adhesion molecule mediates the repulsion of neurons by the extracellular matrix glycoprotein J1-160/180. Neuron. 1993 Jan;10(1):69-82. doi: 10.1016/0896-6273(93)90243-k. PMID:7678967 doi:http://dx.doi.org/10.1016/0896-6273(93)90243-k

[4] Chataigner LMP, Gogou C, den Boer MA, Frias CP, Thies-Weesie DME, Granneman JCM, Heck AJR, Meijer DH, Janssen BJC. Structural insights into the contactin 1 - neurofascin 155 adhesion complex. Nat Commun. 2022 Nov 3;13(1):6607. doi: 10.1038/s41467-022-34302-9. PMID:36329006 doi:http://dx.doi.org/10.1038/s41467-022-34302-9

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