1xt3: Difference between revisions
New page: left|200px<br /><applet load="1xt3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xt3, resolution 2.4Å" /> '''Structure Basis of Ve... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1xt3.gif|left|200px]]<br /><applet load="1xt3" size=" | [[Image:1xt3.gif|left|200px]]<br /><applet load="1xt3" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1xt3, resolution 2.4Å" /> | caption="1xt3, resolution 2.4Å" /> | ||
'''Structure Basis of Venom Citrate-Dependent Heparin Sulfate-Mediated Cell Surface Retention of Cobra Cardiotoxin A3'''<br /> | '''Structure Basis of Venom Citrate-Dependent Heparin Sulfate-Mediated Cell Surface Retention of Cobra Cardiotoxin A3'''<br /> | ||
==Overview== | ==Overview== | ||
Anionic citrate is a major component of venom, but the role of venom | Anionic citrate is a major component of venom, but the role of venom citrate in toxicity other than its inhibitory effect on the cation-dependent action of venom toxins is poorly understood. By immobilizing Chinese hamster ovary cells in microcapillary tubes and heparin on sensor chips, we demonstrated that heparan sulfate-mediated cell retention of the major cardiotoxin (CTX) from the Taiwan cobra, CTX A3, near membrane surfaces is citrate-dependent. X-ray determination of a CTX A3-heparin hexasaccharide complex structure at 2.4 A resolution revealed a molecular mechanism for toxin retention in which heparin-induced conformational changes of CTX A3 lead to citrate-mediated dimerization. A citrate ion bound to Lys-23 and Lys-31 near the tip of loop II stabilizes hydrophobic contact of the CTX A3 homodimer at the functionally important loop I and II regions. Additionally, the heparin hexasaccharide interacts with five CTX A3 molecules in the crystal structure, providing another mechanism whereby the toxin establishes a complex network of interactions that result in a strong interaction with cell surfaces presenting heparan sulfate. Our results suggest a novel role for venom citrate in biological activity and reveal a structural model that explains cell retention of cobra CTX A3 through heparan sulfate-CTX interactions. | ||
==About this Structure== | ==About this Structure== | ||
1XT3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Naja_atra Naja atra] with CIT as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1XT3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Naja_atra Naja atra] with <scene name='pdbligand=CIT:'>CIT</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XT3 OCA]. | ||
==Reference== | ==Reference== | ||
| Line 13: | Line 13: | ||
[[Category: Naja atra]] | [[Category: Naja atra]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Chen, C | [[Category: Chen, C J.]] | ||
[[Category: Guan, H | [[Category: Guan, H H.]] | ||
[[Category: Huang, W | [[Category: Huang, W N.]] | ||
[[Category: Lee, S | [[Category: Lee, S C.]] | ||
[[Category: Wang, C | [[Category: Wang, C H.]] | ||
[[Category: Wu, W | [[Category: Wu, W G.]] | ||
[[Category: CIT]] | [[Category: CIT]] | ||
[[Category: citrate]] | [[Category: citrate]] | ||
| Line 24: | Line 24: | ||
[[Category: heparin]] | [[Category: heparin]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:58:27 2008'' | ||
Revision as of 16:58, 21 February 2008
|
Structure Basis of Venom Citrate-Dependent Heparin Sulfate-Mediated Cell Surface Retention of Cobra Cardiotoxin A3
OverviewOverview
Anionic citrate is a major component of venom, but the role of venom citrate in toxicity other than its inhibitory effect on the cation-dependent action of venom toxins is poorly understood. By immobilizing Chinese hamster ovary cells in microcapillary tubes and heparin on sensor chips, we demonstrated that heparan sulfate-mediated cell retention of the major cardiotoxin (CTX) from the Taiwan cobra, CTX A3, near membrane surfaces is citrate-dependent. X-ray determination of a CTX A3-heparin hexasaccharide complex structure at 2.4 A resolution revealed a molecular mechanism for toxin retention in which heparin-induced conformational changes of CTX A3 lead to citrate-mediated dimerization. A citrate ion bound to Lys-23 and Lys-31 near the tip of loop II stabilizes hydrophobic contact of the CTX A3 homodimer at the functionally important loop I and II regions. Additionally, the heparin hexasaccharide interacts with five CTX A3 molecules in the crystal structure, providing another mechanism whereby the toxin establishes a complex network of interactions that result in a strong interaction with cell surfaces presenting heparan sulfate. Our results suggest a novel role for venom citrate in biological activity and reveal a structural model that explains cell retention of cobra CTX A3 through heparan sulfate-CTX interactions.
About this StructureAbout this Structure
1XT3 is a Single protein structure of sequence from Naja atra with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis of citrate-dependent and heparan sulfate-mediated cell surface retention of cobra cardiotoxin A3., Lee SC, Guan HH, Wang CH, Huang WN, Tjong SC, Chen CJ, Wu WG, J Biol Chem. 2005 Mar 11;280(10):9567-77. Epub 2004 Dec 6. PMID:15590643
Page seeded by OCA on Thu Feb 21 15:58:27 2008