SASDB55: Glycosylated myelin-associated glycoprotein full extracellular do...

Basic information

• Entry: Database: SASBDB / ID: SASDB55

Sample

Glycosylated myelin-associated glycoprotein full extracellular domain (immunoglobulin domains 1-5)

• Myelin-associated glycoprotein Ig domains 1-5 (protein), MAG, Mus musculus

Function / homology

Function:

mesaxon / Axonal growth inhibition (RHOA activation) / compact myelin / ganglioside GT1b binding / central nervous system myelination / sialic acid binding / positive regulation of myelination / myelin sheath adaxonal region / central nervous system myelin formation / negative regulation of axon extension / cell-cell adhesion via plasma-membrane adhesion molecules / paranode region of axon / Schmidt-Lanterman incisure / positive regulation of astrocyte differentiation / 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 #554: ; Type: mix / Software: OLIGOMER / Radius of dummy atoms: 1.90 A / Chi-square value: 16.4025; Search similar-shape structures of this assembly by Omokage search (details)
• Model #555: ; Type: atomic / Software: OLIGOMER / Radius of dummy atoms: 1.90 A / Chi-square value: 16.4025; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Glycosylated myelin-associated glycoprotein full extracellular domain (immunoglobulin domains 1-5); Specimen concentration: 3.38 mg/ml
• Buffer: Name: HEPES / Concentration: 25.00 mM / pH: 7.5 / Composition: 150 mM NaCl

Entity #355

Name: MAG / Type: protein / Description: Myelin-associated glycoprotein Ig domains 1-5 / Formula weight: 53.963 / Num. of mol.: 2 / 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 QRATAFNLSV 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 synchrotronSynchrotron / Wavelength: 0.93 Å / Dist. spec. to detc.: 2.43 mm
• Detector: Name: Pilatus 1M

Scan

Title: Glycosylated MAG (extracellular domain Ig1-5) / Measurement date: Sep 11, 2014 / Storage temperature: 20 °C / Cell temperature: 20 °C / Exposure time: 2 sec. / Number of frames: 9 / Unit: 1/nm /

	Min	Max
Q	0.0363	4.9693

Distance distribution function P(R)

Sofotware P(R): GNOM 4.5a / Number of points: 231 /

	Min	Max
Q	0.08368	1.173
P(R) point	11	241
R	0	23.79

Result

Type of curve: single_conc
Comments: The model fit displayed in this entry represents the volume fraction weighted contributions of the myelin-associated glycoprotein monomer and dimer structures (determined from X-ray crystallography) present in the sample.

	Experimental	Porod
MW	77 kDa	-
Volume	-	177 nm3

	P(R)	P(R) error	Guinier	Guinier error
Forward scattering, I0	76.61	0.08	76.79	0.098
Radius of gyration, Rg	6.99 nm	0.009	6.8 nm	0.22

	Min	Max
D	-	23.79
Guinier point	11	28