SASDB36: Glycosylated myelin-associated glycoprotein full extracellular do...

Basic information

• Entry: Database: SASBDB / ID: SASDB36

Sample

Glycosylated myelin-associated glycoprotein full extracellular domain (Ig1-5) N406Q mutant

• Myelin-associated glycoprotein (20-508; N406Q mutant) (protein), MAG, Mus musculus

Function / homology

Function:

mesaxon / Axonal growth inhibition (RHOA activation) / Basigin interactions / ganglioside GT1b binding / central nervous system myelination / sialic acid binding / myelin sheath adaxonal region / central nervous system myelin formation / positive regulation of myelination / negative regulation of axon extension / cell-cell adhesion via plasma-membrane adhesion molecules / paranode region of axon / positive regulation of astrocyte differentiation / Schmidt-Lanterman incisure / axon regeneration / transmission of nerve impulse / negative regulation of neuron differentiation / myelination / cellular response to mechanical stimulus / negative regulation of neuron projection development / myelin sheath / carbohydrate binding / negative regulation of neuron apoptotic process / cell adhesion / membrane raft / signaling receptor binding / protein kinase binding / protein homodimerization activity / plasma membrane

Domain/homology:

: / CD80-like, immunoglobulin C2-set / CD80-like C2-set immunoglobulin domain / Immunoglobulin domain / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Immunoglobulin subtype / Immunoglobulin / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold

Component:

Myelin-associated glycoprotein

• Biological species: Mus musculus (house mouse)
• Citation: Journal: Nat Commun / Year: 2016; Title: Structural basis of myelin-associated glycoprotein adhesion and signalling.; Authors: Matti F Pronker / Suzanne Lemstra / Joost Snijder / Albert J R Heck / Dominique M E Thies-Weesie / R Jeroen Pasterkamp / Bert J C Janssen / ; Abstract: Myelin-associated glycoprotein (MAG) is a myelin-expressed cell-adhesion and bi-directional signalling molecule. MAG maintains the myelin-axon spacing by interacting with specific neuronal glycolipids (gangliosides), inhibits axon regeneration and controls myelin formation. The mechanisms underlying MAG adhesion and signalling are unresolved. We present crystal structures of the MAG full ectodomain, which reveal an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5. MAG-oligosaccharide complex structures and biophysical assays show how MAG engages axonal gangliosides at domain Ig1. Two post-translational modifications were identified-N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site-that appear to have regulatory functions. Structure-guided mutations and neurite outgrowth assays demonstrate MAG dimerization and carbohydrate recognition are essential for its regeneration-inhibiting properties. The combination of trans ganglioside binding and cis homodimerization explains how MAG maintains the myelin-axon spacing and provides a mechanism for MAG-mediated bi-directional signalling.

Contact author

• Matti Pronker (Utrecht University, Utrecht, Netherlands)

Models

• Model #570: ; Type: atomic / Software: Crysol (2.8.3) / Radius of dummy atoms: 1.90 A / Chi-square value: 11.888704; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Glycosylated myelin-associated glycoprotein full extracellular domain (Ig1-5) N406Q mutant; Specimen concentration: 2.12 mg/ml
• Buffer: Name: HEPES / Concentration: 20.00 mM / pH: 7.5 / Composition: 150 mM NaCl

Entity #393

Name: MAG / Type: protein
Description: Myelin-associated glycoprotein (20-508; N406Q mutant)
Formula weight: 53.978 / Num. of mol.: 1 / Source: Mus musculus / References: UniProt: P20917
Sequence:

GHWGAWMPST ISAFEGTCVS IPCRFDFPDE LRPAVVHGVW YFNSPYPKNY PPVVFKSRTQ VVHESFQGRS RLLGDLGLRN CTLLLSTLSP ELGGKYYFRG DLGGYNQYTF SEHSVLDIVN TPNIVVPPEV VAGTEVEVSC MVPDNCPELR PELSWLGHEG LGEPTVLGRL REDEGTWVQV SLLHFVPTRE ANGHRLGCQA AFPNTTLQFE GYASLDVKYP PVIVEMNSSV EAIEGSHVSL LCGADSNPPP LLTWMRDGMV LREAVAKSLY LDLEEVTPGE DGVYACLAEN AYGQDNRTVE LSVMYAPWKP TVNGTVVAVE GETVSILCST QSNPDPILTI FKEKQILATV IYESQLQLEL PAVTPEDDGE YWCVAENQYG QRATAFQLSV EFAPIILLES HCAAARDTVQ CLCVVKSNPE PSVAFELPSR NVTVNETERE FVYSERSGLL LTSILTIRGQ AQAPPRVICT SRNLYGTQSL ELPFQGAHR

Experimental information

• Beam: Instrument name: ESRF BM29 / City: Grenoble / 国: France / Type of source: X-ray synchrotron / Wavelength: 0.0992 Å / Dist. spec. to detc.: 2.87 mm
• Detector: Name: Pilatus 1M

Scan

Title: Glycosylated myelin-associated glycoprotein full e / Measurement date: Feb 5, 2016 / Storage temperature: 20 °C / Cell temperature: 20 °C / Exposure time: 1 sec. / Number of frames: 9 / Unit: 1/nm /

	Min	Max
Q	0.0329	4.9448

Distance distribution function P(R)

Sofotware P(R): GNOM 4.5a / Number of points: 214 /

	Min	Max
Q	0.08944	1.093
P(R) point	13	226
R	0	25.58

Result

Type of curve: single_conc
Comments: Myelin-associated glycoprotein (MAG) full extracellular domain (immunoglobulin domains 1-5) with an N406Q mutation that should, based on the crystal structure, enhance MAG dimerization by removing an N-linked glycan that clashes with its symmetry mate.

	Experimental	Standard	Porod
MW	63.7 kDa	82 kDa	112.74 kDa
Volume	-	-	193.23 nm3

	P(R)	Guinier
Forward scattering, I0	82.23	82
Radius of gyration, Rg	7.6 nm	7.3 nm

	Min	Max
D	-	25.6
Guinier point	13	27