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(New page: 200px<br /><applet load="1wlf" size="450" color="white" frame="true" align="right" spinBox="true" caption="1wlf, resolution 2.05&Aring;" /> '''Structure of the N-t...)
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'''Structure of the N-terminal domain of PEX1 AAA-ATPase: Characterization of a putative adaptor-binding domain'''<br />
'''Structure of the N-terminal domain of PEX1 AAA-ATPase: Characterization of a putative adaptor-binding domain'''<br />
==Overview==
==Overview==
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Peroxisomes are responsible for several pathways in primary metabolism, including beta-oxidation and lipid biosynthesis. PEX1 and PEX6 are, hexameric AAA-type ATPases, both of which are indispensable in targeting, over 50 peroxisomal resident proteins from the cytosol to the peroxisomes., Although the tandem AAA-ATPase domains in the central region of PEX1 and, PEX6 are highly similar, the N-terminal sequences are unique. To better, understand the distinct molecular function of these two proteins, we, analyzed the unique N-terminal domain (NTD) of PEX1. Extensive, computational analysis revealed weak similarity (&lt;10% identity) of PEX1, NTD to the N-terminal domains of other membrane-related type II, AAA-ATPases, such as VCP (p97) and NSF. We have determined the crystal, structure of mouse PEX1 NTD at 2.05-A resolution, which clearly, demonstrated that the domain belongs to the double-psi-barrel fold family, found in the other AAA-ATPases. The N-domains of both VCP and NSF are, structural neighbors of PEX1 NTD with a 2.7- and 2.1-A root mean square, deviation of backbone atoms, respectively. Our findings suggest that the, supradomain architecture, which is composed of a single N-terminal domain, followed by tandem AAA domains, is a common feature of organellar, membrane-associating AAA-ATPases. We propose that PEX1 functions as a, protein unfoldase in peroxisomal biogenesis, using its N-terminal putative, adaptor-binding domain.
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Peroxisomes are responsible for several pathways in primary metabolism, including beta-oxidation and lipid biosynthesis. PEX1 and PEX6 are hexameric AAA-type ATPases, both of which are indispensable in targeting over 50 peroxisomal resident proteins from the cytosol to the peroxisomes. Although the tandem AAA-ATPase domains in the central region of PEX1 and PEX6 are highly similar, the N-terminal sequences are unique. To better understand the distinct molecular function of these two proteins, we analyzed the unique N-terminal domain (NTD) of PEX1. Extensive computational analysis revealed weak similarity (&lt;10% identity) of PEX1 NTD to the N-terminal domains of other membrane-related type II AAA-ATPases, such as VCP (p97) and NSF. We have determined the crystal structure of mouse PEX1 NTD at 2.05-A resolution, which clearly demonstrated that the domain belongs to the double-psi-barrel fold family found in the other AAA-ATPases. The N-domains of both VCP and NSF are structural neighbors of PEX1 NTD with a 2.7- and 2.1-A root mean square deviation of backbone atoms, respectively. Our findings suggest that the supradomain architecture, which is composed of a single N-terminal domain followed by tandem AAA domains, is a common feature of organellar membrane-associating AAA-ATPases. We propose that PEX1 functions as a protein unfoldase in peroxisomal biogenesis, using its N-terminal putative adaptor-binding domain.
==About this Structure==
==About this Structure==
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1WLF is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1WLF OCA].
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1WLF is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WLF OCA].
==Reference==
==Reference==
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[[Category: n-terminal domain]]
[[Category: n-terminal domain]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 00:10:38 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:45:37 2008''

Revision as of 13:45, 21 February 2008


1wlf, resolution 2.05Å

Drag the structure with the mouse to rotate

Structure of the N-terminal domain of PEX1 AAA-ATPase: Characterization of a putative adaptor-binding domain

Overview

Peroxisomes are responsible for several pathways in primary metabolism, including beta-oxidation and lipid biosynthesis. PEX1 and PEX6 are hexameric AAA-type ATPases, both of which are indispensable in targeting over 50 peroxisomal resident proteins from the cytosol to the peroxisomes. Although the tandem AAA-ATPase domains in the central region of PEX1 and PEX6 are highly similar, the N-terminal sequences are unique. To better understand the distinct molecular function of these two proteins, we analyzed the unique N-terminal domain (NTD) of PEX1. Extensive computational analysis revealed weak similarity (<10% identity) of PEX1 NTD to the N-terminal domains of other membrane-related type II AAA-ATPases, such as VCP (p97) and NSF. We have determined the crystal structure of mouse PEX1 NTD at 2.05-A resolution, which clearly demonstrated that the domain belongs to the double-psi-barrel fold family found in the other AAA-ATPases. The N-domains of both VCP and NSF are structural neighbors of PEX1 NTD with a 2.7- and 2.1-A root mean square deviation of backbone atoms, respectively. Our findings suggest that the supradomain architecture, which is composed of a single N-terminal domain followed by tandem AAA domains, is a common feature of organellar membrane-associating AAA-ATPases. We propose that PEX1 functions as a protein unfoldase in peroxisomal biogenesis, using its N-terminal putative adaptor-binding domain.

About this Structure

1WLF is a Protein complex structure of sequences from Mus musculus with as ligand. Full crystallographic information is available from OCA.

Reference

Structure of the N-terminal domain of PEX1 AAA-ATPase. Characterization of a putative adaptor-binding domain., Shiozawa K, Maita N, Tomii K, Seto A, Goda N, Akiyama Y, Shimizu T, Shirakawa M, Hiroaki H, J Biol Chem. 2004 Nov 26;279(48):50060-8. Epub 2004 Aug 24. PMID:15328346

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