1sk3

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==Overview==
==Overview==
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Peptidoglycan recognition proteins (PGRPs) are pattern recognition, receptors of the innate immune system that bind, and in some cases, hydrolyze, peptidoglycans (PGNs) on bacterial cell walls. These molecules, which are highly conserved from insects to mammals, participate in host, defense against both Gram-positive and Gram-negative bacteria. We report, the crystal structure of the C-terminal PGN-binding domain of human, PGRP-Ialpha in two oligomeric states, monomer and dimer, to resolutions of, 2.80 and 1.65 A, respectively. In contrast to PGRPs with PGN-lytic amidase, activity, no zinc ion is present in the PGN-binding site of human, PGRP-Ialpha. The structure reveals that PGRPs exhibit extensive, topological variability in a large hydrophobic groove, located opposite, the PGN-binding site, which may recognize host effector proteins or, microbial ligands other than PGN. We also show that full-length, PGRP-Ialpha comprises two tandem PGN-binding domains. These domains differ, at most potential PGN-contacting positions, implying different fine, specificities. Dimerization of PGRP-Ialpha, which occurs through, three-dimensional domain swapping, is mediated by specific binding of, sodium ions to a flexible hinge loop, stabilizing the conformation found, in the dimer. We further demonstrate sodium-dependent dimerization of, PGRP-Ialpha in solution, suggesting a possible mechanism for modulating, PGRP activity through the formation of multivalent adducts.
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Peptidoglycan recognition proteins (PGRPs) are pattern recognition receptors of the innate immune system that bind, and in some cases hydrolyze, peptidoglycans (PGNs) on bacterial cell walls. These molecules, which are highly conserved from insects to mammals, participate in host defense against both Gram-positive and Gram-negative bacteria. We report the crystal structure of the C-terminal PGN-binding domain of human PGRP-Ialpha in two oligomeric states, monomer and dimer, to resolutions of 2.80 and 1.65 A, respectively. In contrast to PGRPs with PGN-lytic amidase activity, no zinc ion is present in the PGN-binding site of human PGRP-Ialpha. The structure reveals that PGRPs exhibit extensive topological variability in a large hydrophobic groove, located opposite the PGN-binding site, which may recognize host effector proteins or microbial ligands other than PGN. We also show that full-length PGRP-Ialpha comprises two tandem PGN-binding domains. These domains differ at most potential PGN-contacting positions, implying different fine specificities. Dimerization of PGRP-Ialpha, which occurs through three-dimensional domain swapping, is mediated by specific binding of sodium ions to a flexible hinge loop, stabilizing the conformation found in the dimer. We further demonstrate sodium-dependent dimerization of PGRP-Ialpha in solution, suggesting a possible mechanism for modulating PGRP activity through the formation of multivalent adducts.
==About this Structure==
==About this Structure==
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[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Guan, R.]]
[[Category: Guan, R.]]
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[[Category: Malchiodi, E.L.]]
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[[Category: Malchiodi, E L.]]
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[[Category: Mariuzza, R.A.]]
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[[Category: Mariuzza, R A.]]
[[Category: Qian, W.]]
[[Category: Qian, W.]]
[[Category: Schuck, P.]]
[[Category: Schuck, P.]]
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[[Category: alpha/beta mix]]
[[Category: alpha/beta mix]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:53:57 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:02:18 2008''

Revision as of 13:02, 21 February 2008

Image:1sk3.jpg

1sk3, resolution 2.80Å

Drag the structure with the mouse to rotate

Crystal structure of the C-terminal peptidoglycan-binding domain of human peptidoglycan recognition protein Ialpha

Overview

Peptidoglycan recognition proteins (PGRPs) are pattern recognition receptors of the innate immune system that bind, and in some cases hydrolyze, peptidoglycans (PGNs) on bacterial cell walls. These molecules, which are highly conserved from insects to mammals, participate in host defense against both Gram-positive and Gram-negative bacteria. We report the crystal structure of the C-terminal PGN-binding domain of human PGRP-Ialpha in two oligomeric states, monomer and dimer, to resolutions of 2.80 and 1.65 A, respectively. In contrast to PGRPs with PGN-lytic amidase activity, no zinc ion is present in the PGN-binding site of human PGRP-Ialpha. The structure reveals that PGRPs exhibit extensive topological variability in a large hydrophobic groove, located opposite the PGN-binding site, which may recognize host effector proteins or microbial ligands other than PGN. We also show that full-length PGRP-Ialpha comprises two tandem PGN-binding domains. These domains differ at most potential PGN-contacting positions, implying different fine specificities. Dimerization of PGRP-Ialpha, which occurs through three-dimensional domain swapping, is mediated by specific binding of sodium ions to a flexible hinge loop, stabilizing the conformation found in the dimer. We further demonstrate sodium-dependent dimerization of PGRP-Ialpha in solution, suggesting a possible mechanism for modulating PGRP activity through the formation of multivalent adducts.

About this Structure

1SK3 is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.

Reference

Crystal structure of the C-terminal peptidoglycan-binding domain of human peptidoglycan recognition protein Ialpha., Guan R, Malchiodi EL, Wang Q, Schuck P, Mariuzza RA, J Biol Chem. 2004 Jul 23;279(30):31873-82. Epub 2004 May 12. PMID:15140887

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