SASDA86: NetrinVIV DCC56(M933R) complex (Netrin-1, NetrinVIV + Deleted in ...

Basic information

Entry

Database: SASBDB / ID: SASDA86

Sample

NetrinVIV DCC56(M933R) complex

• Netrin-1 (protein), NetrinVIV, Homo sapiens
• Deleted in Colorectal Cancer (FN5 & FN6) M933R mutant (protein), DCC56 (M933R), Homo sapiens

Function / homology

Function:

regulation of glial cell migration / DSCAM interactions / chemorepulsion of axon / anterior/posterior axon guidance / Cdc42 protein signal transduction / Role of second messengers in netrin-1 signaling / Netrin-1 signaling / Regulation of commissural axon pathfinding by SLIT and ROBO / motor neuron migration / negative regulation of axon extension / Netrin mediated repulsion signals / substrate-dependent cell migration, cell extension / mammary gland duct morphogenesis / nuclear migration / positive regulation of cell motility / DCC mediated attractive signaling / inner ear morphogenesis / regulation of synapse assembly / basement membrane / glial cell proliferation / positive regulation of axon extension / positive regulation of glial cell proliferation / cell-cell adhesion / actin cytoskeleton / Ras protein signal transduction / DNA-binding transcription factor activity, RNA polymerase II-specific / RNA polymerase II cis-regulatory region sequence-specific DNA binding / regulation of transcription by RNA polymerase II / apoptotic process / extracellular region / nucleoplasm / cytosol

Domain/homology:

: / Laminin, N-terminal / Laminin N-terminal (Domain VI) / Laminin N-terminal domain profile. / Laminin N-terminal domain (domain VI) / Laminin-type EGF-like (LE) domain profile. / Laminin-type EGF-like (LE) domain signature. / Laminin-type epidermal growth factor-like domai / Laminin EGF domain / Laminin-type EGF domain / Netrin C-terminal Domain / Netrin module, non-TIMP type / UNC-6/NTR/C345C module / Netrin domain / NTR domain profile. / Tissue inhibitor of metalloproteinases-like, OB-fold / EGF-like domain signature 1. / Galactose-binding-like domain superfamily

Component:

Netrin-1

• Biological species: Homo sapiens (human)
• Citation: Journal: Neuron / Year: 2014; Title: The crystal structure of netrin-1 in complex with DCC reveals the bifunctionality of netrin-1 as a guidance cue.; Authors: Lorenzo I Finci / Nina Krüger / Xiaqin Sun / Jie Zhang / Magda Chegkazi / Yu Wu / Gundolf Schenk / Haydyn D T Mertens / Dmitri I Svergun / Yan Zhang / Jia-Huai Wang / Rob Meijers / ; Abstract: Netrin-1 is a guidance cue that can trigger either attraction or repulsion effects on migrating axons of neurons, depending on the repertoire of receptors available on the growth cone. How a single chemotropic molecule can act in such contradictory ways has long been a puzzle at the molecular level. Here we present the crystal structure of netrin-1 in complex with the Deleted in Colorectal Cancer (DCC) receptor. We show that one netrin-1 molecule can simultaneously bind to two DCC molecules through a DCC-specific site and through a unique generic receptor binding site, where sulfate ions staple together positively charged patches on both DCC and netrin-1. Furthermore, we demonstrate that UNC5A can replace DCC on the generic receptor binding site to switch the response from attraction to repulsion. We propose that the modularity of binding allows for the association of other netrin receptors at the generic binding site, eliciting alternative turning responses.

Contact author

• Haydyn Mertens (EMBL-Hamburg, European Molecular Biology Laboratory (EMBL) - Hamburg outstation, Notkestraße 85, Geb. 25A, 22607 Hamburg, Deutschland, Germany)

Models

Sample

• Sample: Name: NetrinVIV DCC56(M933R) complex / Specimen concentration: 0.30-3.90 / Entity id: 113 / 118
• Buffer: Name: MES / Concentration: 25.00 mM / pH: 7 / Comment: MES/TRIS; Composition: NaCl 200.000 mM, Tris 50.000 mM, (NH4)2(SO4) 0.200 M ammonium sulfate, CaCl2 1.000 mM calcium chloride

Entity #113

Name: NetrinVIV / Type: protein / Description: Netrin-1 / Formula weight: 49.1 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: O95631
Sequence:

GPGLSMFAGQ AAQPDPCSDE NGHPRRCIPD FVNAAFGKDV RVSSTCGRPP ARYCVVSERG EERLRSCHLC NASDPKKAHP PAFLTDLNNP HNLTCWQSEN YLQFPHNVTL TLSLGKKFEV TYVSLQFCSP RPESMAIYKS MDYGRTWVPF QFYSTQCRKM YNRPHRAPIT KQNEQEAVCT DSHTDMRPLS GGLIAFSTLD GRPSAHDFDN SPVLQDWVTA TDIRVAFSRL HTFGDENEDD SELARDSYFY AVSDLQVGGR CKCNGHAARC VRDRDDSLVC DCRHNTAGPE CDRCKPFHYD RPWQRATARE ANECVACNCN LHARRCRFNM ELYKLSGRKS GGVCLNCRHN TAGRHCHYCK EGYYRDMGKP ITHRKACKAC DCHPVGAAGK TCNQTTGQCP CKDGVTGITC NRCAKGYQQS RSPIAPCIKE LHHHHHH

Entity #118

Name: DCC56 (M933R) / Type: protein
Description: Deleted in Colorectal Cancer (FN5 & FN6) M933R mutant
Formula weight: 25.5 / Num. of mol.: 1 / Source: Homo sapiens
Sequence:

MLPPVGVQAV ALTHDAVRVS WADNSVPKNQ KTSEVRLYTV RWRTSFSASA KYKSEDTTSL SYTATGLKPN TMYEFSVMVT KNRRSSTWSR TAHATTYEAA PTSAPKDLTV ITREGKPRAV IVSWQPPLEA NGKITAYILF YTLDKNIPID DWIMETISGD RLTHQIMDLN LDTMYYFRIQ ARNSKGVGPL SDPILFRTLK LEVLFQGPGG HHHHHHGGWS HPQFEK

Experimental information

• Beam: Instrument name: PETRA III P12 / City: Hamburg / 国: Germany / Type of source: X-ray synchrotron / Wavelength: 0.12 Å / Dist. spec. to detc.: 3.1 mm
• Detector: Name: Pilatus 2M

Scan

Title: NetrinVIV DCC56(M933R) complex / Measurement date: Aug 26, 2013 / Storage temperature: 10 °C / Cell temperature: 10 °C / Exposure time: 0.05 sec. / Number of frames: 20 / Unit: 1/nm /

	Min	Max
Q	0.0516	3.4968

Distance distribution function P(R)

Sofotware P(R): GNOM 4.5a / Number of points: 474 /

	Min	Max
Q	0.1265	2.014
P(R) point	38	511
R	0	13.9

Result

Type of curve: single_conc /

	Experimental	Porod
MW	42 kDa	-
Volume	-	95 nm3

	P(R)	Guinier
Forward scattering, I0	1260	1270
Radius of gyration, Rg	4 nm	4 nm

	Min	Max
D	-	14
Guinier point	38	124