2h8l
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The synthesis of proteins in the endoplasmic reticulum (ER) is limited by | + | The synthesis of proteins in the endoplasmic reticulum (ER) is limited by the rate of correct disulfide bond formation. This process is carried out by protein disulfide isomerases, a family of ER proteins which includes general enzymes such as PDI that recognize unfolded proteins and others that are selective for specific proteins or classes. Using small-angle X-ray scattering and X-ray crystallography, we report the structure of a selective isomerase, ERp57, and its interactions with the lectin chaperone calnexin. Using isothermal titration calorimetry and NMR spectroscopy, we show that the b' domain of ERp57 binds calnexin with micromolar affinity through a conserved patch of basic residues. Disruption of this binding site by mutagenesis abrogates folding of RNase B in an in vitro assay. The relative positions of the ERp57 catalytic sites and calnexin binding site suggest that activation by calnexin is due to substrate recruitment rather than a direct stimulation of ERp57 oxidoreductase activity. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Gehring, K.]] | [[Category: Gehring, K.]] | ||
[[Category: Kozlov, G.]] | [[Category: Kozlov, G.]] | ||
| - | [[Category: Schrag, J | + | [[Category: Schrag, J D.]] |
[[Category: thioredoxin-like fold]] | [[Category: thioredoxin-like fold]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:39:18 2008'' |
Revision as of 15:39, 21 February 2008
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Crystal structure of the bb' fragment of ERp57
Overview
The synthesis of proteins in the endoplasmic reticulum (ER) is limited by the rate of correct disulfide bond formation. This process is carried out by protein disulfide isomerases, a family of ER proteins which includes general enzymes such as PDI that recognize unfolded proteins and others that are selective for specific proteins or classes. Using small-angle X-ray scattering and X-ray crystallography, we report the structure of a selective isomerase, ERp57, and its interactions with the lectin chaperone calnexin. Using isothermal titration calorimetry and NMR spectroscopy, we show that the b' domain of ERp57 binds calnexin with micromolar affinity through a conserved patch of basic residues. Disruption of this binding site by mutagenesis abrogates folding of RNase B in an in vitro assay. The relative positions of the ERp57 catalytic sites and calnexin binding site suggest that activation by calnexin is due to substrate recruitment rather than a direct stimulation of ERp57 oxidoreductase activity.
About this Structure
2H8L is a Single protein structure of sequence from Homo sapiens. Active as Protein disulfide-isomerase, with EC number 5.3.4.1 Full crystallographic information is available from OCA.
Reference
Crystal structure of the bb' domains of the protein disulfide isomerase ERp57., Kozlov G, Maattanen P, Schrag JD, Pollock S, Cygler M, Nagar B, Thomas DY, Gehring K, Structure. 2006 Aug;14(8):1331-9. PMID:16905107
Page seeded by OCA on Thu Feb 21 17:39:18 2008
