1zza
From Proteopedia
(New page: 200px<br /> <applet load="1zza" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zza" /> '''Solution NMR Structure of the Membrane Prot...) |
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'''Solution NMR Structure of the Membrane Protein Stannin'''<br /> | '''Solution NMR Structure of the Membrane Protein Stannin'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Organotin compounds or alkyltins are ubiquitous environmental toxins that | + | Organotin compounds or alkyltins are ubiquitous environmental toxins that have been implicated in cellular death. Unlike other xenobiotic compounds, such as organomercurials and organoleads, alkyltins activate apoptotic cascades at low concentrations. Trimethyltin (TMT) chloride is amongst the most toxic organotin compounds, and is known to selectively inflict injury to specific regions of the brain. Stannin (SNN), an 88-residue mitochondrial membrane protein, has been identified as the specific marker for neuronal cell apoptosis induced by TMT intoxication. This high specificity of TMT makes SNN an ideal model system for understanding the mechanism of organotin neurotoxicity at a molecular level. Here, we report the three-dimensional structure and dynamics of SNN in detergent micelles, and its topological orientation in lipid bilayers as determined by solution and solid-state NMR spectroscopy. We found that SNN is a monotopic membrane protein composed of three domains: a single transmembrane helix (residues 10-33) that transverses the lipid bilayer at approximately a 20 degrees angle with respect to the membrane normal; a 28 residue unstructured linker, which includes a conserved CXC metal-binding motif and a putative 14-3-3zeta binding domain; and a distorted cytoplasmic helix (residues 61-79) that is partially absorbed into the plane of the lipid bilayer with a tilt angle of approximately 80 degrees from the membrane normal. The structure and architecture of SNN within the lipid environment provides insight about how this protein transmits toxic insults caused by TMT across the membrane. |
==About this Structure== | ==About this Structure== | ||
| - | 1ZZA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1ZZA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZZA OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Buck-Koehntop, B | + | [[Category: Buck-Koehntop, B A.]] |
| - | [[Category: Buffy, J | + | [[Category: Buffy, J J.]] |
[[Category: Mascioni, A.]] | [[Category: Mascioni, A.]] | ||
[[Category: Veglia, G.]] | [[Category: Veglia, G.]] | ||
[[Category: helix]] | [[Category: helix]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:20:32 2008'' |
Revision as of 14:20, 21 February 2008
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Solution NMR Structure of the Membrane Protein Stannin
Overview
Organotin compounds or alkyltins are ubiquitous environmental toxins that have been implicated in cellular death. Unlike other xenobiotic compounds, such as organomercurials and organoleads, alkyltins activate apoptotic cascades at low concentrations. Trimethyltin (TMT) chloride is amongst the most toxic organotin compounds, and is known to selectively inflict injury to specific regions of the brain. Stannin (SNN), an 88-residue mitochondrial membrane protein, has been identified as the specific marker for neuronal cell apoptosis induced by TMT intoxication. This high specificity of TMT makes SNN an ideal model system for understanding the mechanism of organotin neurotoxicity at a molecular level. Here, we report the three-dimensional structure and dynamics of SNN in detergent micelles, and its topological orientation in lipid bilayers as determined by solution and solid-state NMR spectroscopy. We found that SNN is a monotopic membrane protein composed of three domains: a single transmembrane helix (residues 10-33) that transverses the lipid bilayer at approximately a 20 degrees angle with respect to the membrane normal; a 28 residue unstructured linker, which includes a conserved CXC metal-binding motif and a putative 14-3-3zeta binding domain; and a distorted cytoplasmic helix (residues 61-79) that is partially absorbed into the plane of the lipid bilayer with a tilt angle of approximately 80 degrees from the membrane normal. The structure and architecture of SNN within the lipid environment provides insight about how this protein transmits toxic insults caused by TMT across the membrane.
About this Structure
1ZZA is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure, dynamics, and membrane topology of stannin: a mediator of neuronal cell apoptosis induced by trimethyltin chloride., Buck-Koehntop BA, Mascioni A, Buffy JJ, Veglia G, J Mol Biol. 2005 Dec 2;354(3):652-65. Epub 2005 Sep 30. PMID:16246365
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