3bju
From Proteopedia
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caption="3bju, resolution 2.31Å" /> | caption="3bju, resolution 2.31Å" /> | ||
'''Crystal Structure of tetrameric form of human lysyl-tRNA synthetase'''<br /> | '''Crystal Structure of tetrameric form of human lysyl-tRNA synthetase'''<br /> | ||
| + | |||
| + | ==Overview== | ||
| + | In mammals, many aminoacyl-tRNA synthetases are bound together in a multisynthetase complex (MSC) as a reservoir of procytokines and regulation molecules for functions beyond aminoacylation. The alpha(2) homodimeric lysyl-tRNA synthetase (LysRS) is tightly bound in the MSC and, under specific conditions, is secreted to trigger a proinflammatory response. Results by others suggest that alpha(2) LysRS is tightly bound into the core of the MSC with homodimeric beta(2) p38, a scaffolding protein that itself is multifunctional. Not understood is how the two dimeric proteins combine to make a presumptive alpha(2)beta(2) heterotetramer and, in particular, the location of the surfaces on LysRS that would accommodate the p38 interactions. Here we present a 2.3-A crystal structure of a tetrameric form of human LysRS. The relatively loose (as seen in solution) tetramer interface is assembled from two eukaryote-specific sequences, one in the catalytic- and another in the anticodon-binding domain. This same interface is predicted to provide unique determinants for interaction with p38. The analyses suggest how the core of the MSC is assembled and, more generally, that interactions and functions of synthetases can be built and regulated through dynamic protein-protein interfaces. These interfaces are created from small adaptations to what is otherwise a highly conserved (through evolution) polypeptide sequence. | ||
==About this Structure== | ==About this Structure== | ||
3BJU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=LYS:'>LYS</scene> and <scene name='pdbligand=ATP:'>ATP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Lysine--tRNA_ligase Lysine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.6 6.1.1.6] Known structural/functional Sites: <scene name='pdbsite=AC1:Ca+Binding+Site+For+Residue+B+606'>AC1</scene>, <scene name='pdbsite=AC2:Ca+Binding+Site+For+Residue+B+607'>AC2</scene>, <scene name='pdbsite=AC3:Ca+Binding+Site+For+Residue+B+608'>AC3</scene>, <scene name='pdbsite=AC4:Ca+Binding+Site+For+Residue+C+606'>AC4</scene>, <scene name='pdbsite=AC5:Ca+Binding+Site+For+Residue+C+607'>AC5</scene>, <scene name='pdbsite=AC6:Ca+Binding+Site+For+Residue+C+608'>AC6</scene>, <scene name='pdbsite=AC7:Ca+Binding+Site+For+Residue+D+606'>AC7</scene>, <scene name='pdbsite=AC8:Ca+Binding+Site+For+Residue+D+607'>AC8</scene>, <scene name='pdbsite=AC9:Ca+Binding+Site+For+Residue+D+608'>AC9</scene>, <scene name='pdbsite=BC1:Ca+Binding+Site+For+Residue+A+606'>BC1</scene>, <scene name='pdbsite=BC2:Ca+Binding+Site+For+Residue+A+607'>BC2</scene>, <scene name='pdbsite=BC3:Ca+Binding+Site+For+Residue+A+608'>BC3</scene>, <scene name='pdbsite=BC4:LYS+Binding+Site+For+Residue+B+601'>BC4</scene>, <scene name='pdbsite=BC5:Atp+Binding+Site+For+Residue+B+603'>BC5</scene>, <scene name='pdbsite=BC6:LYS+Binding+Site+For+Residue+C+601'>BC6</scene>, <scene name='pdbsite=BC7:Atp+Binding+Site+For+Residue+C+603'>BC7</scene>, <scene name='pdbsite=BC8:LYS+Binding+Site+For+Residue+D+601'>BC8</scene>, <scene name='pdbsite=BC9:Atp+Binding+Site+For+Residue+D+603'>BC9</scene>, <scene name='pdbsite=CC1:LYS+Binding+Site+For+Residue+A+601'>CC1</scene> and <scene name='pdbsite=CC2:Atp+Binding+Site+For+Residue+A+603'>CC2</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BJU OCA]. | 3BJU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=LYS:'>LYS</scene> and <scene name='pdbligand=ATP:'>ATP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Lysine--tRNA_ligase Lysine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.6 6.1.1.6] Known structural/functional Sites: <scene name='pdbsite=AC1:Ca+Binding+Site+For+Residue+B+606'>AC1</scene>, <scene name='pdbsite=AC2:Ca+Binding+Site+For+Residue+B+607'>AC2</scene>, <scene name='pdbsite=AC3:Ca+Binding+Site+For+Residue+B+608'>AC3</scene>, <scene name='pdbsite=AC4:Ca+Binding+Site+For+Residue+C+606'>AC4</scene>, <scene name='pdbsite=AC5:Ca+Binding+Site+For+Residue+C+607'>AC5</scene>, <scene name='pdbsite=AC6:Ca+Binding+Site+For+Residue+C+608'>AC6</scene>, <scene name='pdbsite=AC7:Ca+Binding+Site+For+Residue+D+606'>AC7</scene>, <scene name='pdbsite=AC8:Ca+Binding+Site+For+Residue+D+607'>AC8</scene>, <scene name='pdbsite=AC9:Ca+Binding+Site+For+Residue+D+608'>AC9</scene>, <scene name='pdbsite=BC1:Ca+Binding+Site+For+Residue+A+606'>BC1</scene>, <scene name='pdbsite=BC2:Ca+Binding+Site+For+Residue+A+607'>BC2</scene>, <scene name='pdbsite=BC3:Ca+Binding+Site+For+Residue+A+608'>BC3</scene>, <scene name='pdbsite=BC4:LYS+Binding+Site+For+Residue+B+601'>BC4</scene>, <scene name='pdbsite=BC5:Atp+Binding+Site+For+Residue+B+603'>BC5</scene>, <scene name='pdbsite=BC6:LYS+Binding+Site+For+Residue+C+601'>BC6</scene>, <scene name='pdbsite=BC7:Atp+Binding+Site+For+Residue+C+603'>BC7</scene>, <scene name='pdbsite=BC8:LYS+Binding+Site+For+Residue+D+601'>BC8</scene>, <scene name='pdbsite=BC9:Atp+Binding+Site+For+Residue+D+603'>BC9</scene>, <scene name='pdbsite=CC1:LYS+Binding+Site+For+Residue+A+601'>CC1</scene> and <scene name='pdbsite=CC2:Atp+Binding+Site+For+Residue+A+603'>CC2</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BJU OCA]. | ||
| + | |||
| + | ==Reference== | ||
| + | Crystal structure of tetrameric form of human lysyl-tRNA synthetase: Implications for multisynthetase complex formation., Guo M, Ignatov M, Musier-Forsyth K, Schimmel P, Yang XL, Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2331-6. Epub 2008 Feb 13. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18272479 18272479] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Lysine--tRNA ligase]] | [[Category: Lysine--tRNA ligase]] | ||
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[[Category: trna synthetase]] | [[Category: trna synthetase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Mar 14 09:44:05 2008'' |
Revision as of 07:44, 14 March 2008
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Crystal Structure of tetrameric form of human lysyl-tRNA synthetase
Overview
In mammals, many aminoacyl-tRNA synthetases are bound together in a multisynthetase complex (MSC) as a reservoir of procytokines and regulation molecules for functions beyond aminoacylation. The alpha(2) homodimeric lysyl-tRNA synthetase (LysRS) is tightly bound in the MSC and, under specific conditions, is secreted to trigger a proinflammatory response. Results by others suggest that alpha(2) LysRS is tightly bound into the core of the MSC with homodimeric beta(2) p38, a scaffolding protein that itself is multifunctional. Not understood is how the two dimeric proteins combine to make a presumptive alpha(2)beta(2) heterotetramer and, in particular, the location of the surfaces on LysRS that would accommodate the p38 interactions. Here we present a 2.3-A crystal structure of a tetrameric form of human LysRS. The relatively loose (as seen in solution) tetramer interface is assembled from two eukaryote-specific sequences, one in the catalytic- and another in the anticodon-binding domain. This same interface is predicted to provide unique determinants for interaction with p38. The analyses suggest how the core of the MSC is assembled and, more generally, that interactions and functions of synthetases can be built and regulated through dynamic protein-protein interfaces. These interfaces are created from small adaptations to what is otherwise a highly conserved (through evolution) polypeptide sequence.
About this Structure
3BJU is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Lysine--tRNA ligase, with EC number 6.1.1.6 Known structural/functional Sites: , , , , , , , , , , , , , , , , , , and . Full crystallographic information is available from OCA.
Reference
Crystal structure of tetrameric form of human lysyl-tRNA synthetase: Implications for multisynthetase complex formation., Guo M, Ignatov M, Musier-Forsyth K, Schimmel P, Yang XL, Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2331-6. Epub 2008 Feb 13. PMID:18272479
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