1hh8
From Proteopedia
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'''THE ACTIVE N-TERMINAL REGION OF P67PHOX: STRUCTURE AT 1.8 ANGSTROM RESOLUTION AND BIOCHEMICAL CHARACTERIZATIONS OF THE A128V MUTANT IMPLICATED IN CHRONIC GRANULOMATOUS DISEASE''' | '''THE ACTIVE N-TERMINAL REGION OF P67PHOX: STRUCTURE AT 1.8 ANGSTROM RESOLUTION AND BIOCHEMICAL CHARACTERIZATIONS OF THE A128V MUTANT IMPLICATED IN CHRONIC GRANULOMATOUS DISEASE''' | ||
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[[Category: Grizot, S.]] | [[Category: Grizot, S.]] | ||
[[Category: Pebay-Peyroula, E.]] | [[Category: Pebay-Peyroula, E.]] | ||
| - | [[Category: | + | [[Category: Phagocyte oxidase factor]] |
| - | [[Category: | + | [[Category: Repeat]] |
| - | [[Category: | + | [[Category: Sh3 domain]] |
| - | [[Category: | + | [[Category: Tpr repeat]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:50:43 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 15:50, 2 May 2008
THE ACTIVE N-TERMINAL REGION OF P67PHOX: STRUCTURE AT 1.8 ANGSTROM RESOLUTION AND BIOCHEMICAL CHARACTERIZATIONS OF THE A128V MUTANT IMPLICATED IN CHRONIC GRANULOMATOUS DISEASE
Overview
Upon activation, the NADPH oxidase from neutrophils produces superoxide anions in response to microbial infection. This enzymatic complex is activated by association of its cytosolic factors p67(phox), p47(phox), and the small G protein Rac with a membrane-associated flavocytochrome b(558). Here we report the crystal structure of the active N-terminal fragment of p67(phox) at 1.8 A resolution, as well as functional studies of p67(phox) mutants. This N-terminal region (residues 1-213) consists mainly of four TPR (tetratricopeptide repeat) motifs in which the C terminus folds back into a hydrophobic groove formed by the TPR domain. The structure is very similar to that of the inactive truncated form of p67(phox) bound to the small G protein Rac previously reported, but differs by the presence of a short C-terminal helix (residues 187-193) that might be part of the activation domain. All p67(phox) mutants responsible for Chronic Granulomatous Disease (CGD), a severe defect of NADPH oxidase function, are localized in the N-terminal region. We investigated two CGD mutations, G78E and A128V. Surprisingly, the A128V CGD mutant is able to fully activate the NADPH oxidase in vitro at 25 degrees C. However, this point mutation represents a temperature-sensitive defect in p67(phox) that explains its phenotype at physiological temperature.
About this Structure
1HH8 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The active N-terminal region of p67phox. Structure at 1.8 A resolution and biochemical characterizations of the A128V mutant implicated in chronic granulomatous disease., Grizot S, Fieschi F, Dagher MC, Pebay-Peyroula E, J Biol Chem. 2001 Jun 15;276(24):21627-31. Epub 2001 Mar 21. PMID:11262407 Page seeded by OCA on Fri May 2 18:50:43 2008
