SASDA26: DCC56 (Deleted in Colorectal Cancer (FN5 & FN6), dcc56)

Basic information

• Entry: Database: SASBDB / ID: SASDA26

Sample

DCC56

• Deleted in Colorectal Cancer (FN5 & FN6) (protein), dcc56, Homo sapiens

• 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

• Model #166: ; Type: dummy / Software: dammin (5.3) / Radius of dummy atoms: 1.90 A / Chi-square value: 1.442401; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: DCC56 / Specimen concentration: 0.80-9.90
• 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 #114

Name: dcc56 / Type: protein / Description: Deleted in Colorectal Cancer (FN5 & FN6) / Formula weight: 25.5 / Num. of mol.: 1 / Source: Homo sapiens
Sequence:

MLPPVGVQAV ALTHDAVRVS WADNSVPKNQ KTSEVRLYTV RWRTSFSASA KYKSEDTTSL SYTATGLKPN TMYEFSVMVT KNRRSSTWSM 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: DCC56 / 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	0.0768	4.5832

Distance distribution function P(R)

Sofotware P(R): GNOM 5.0 / Number of points: 1658 /

	Min	Max
Q	0.187251	4.54641
P(R) point	1	1658
R	0	11

Result

Type of curve: extrapolated /

	Experimental	Porod	Estimated
MW	27 kDa	24 kDa	-
Volume	-	38 nm3	31

	P(R)	Guinier
Forward scattering, I0	1300	1284
Radius of gyration, Rg	3.4 nm	3.2 nm

	Min	Max
D	-	11
Guinier point	43	128