1zza

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1zza

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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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