Structural basis for the recognition and cleavage of polysialic acid by the bacteriophage K1F tailspike protein EndoNF
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Structural basis for the recognition and cleavage of polysialic acid by the bacteriophage K1F tailspike protein EndoNF. / Schulz, Eike Christian; Schwarzer, David; Frank, Martin; Stummeyer, Katharina; Mühlenhoff, Martina; Dickmanns, Achim; Gerardy-Schahn, Rita; Ficner, Ralf.
In: J MOL BIOL, Vol. 397, No. 1, 19.03.2010, p. 341-51.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Structural basis for the recognition and cleavage of polysialic acid by the bacteriophage K1F tailspike protein EndoNF
AU - Schulz, Eike Christian
AU - Schwarzer, David
AU - Frank, Martin
AU - Stummeyer, Katharina
AU - Mühlenhoff, Martina
AU - Dickmanns, Achim
AU - Gerardy-Schahn, Rita
AU - Ficner, Ralf
N1 - Copyright (c) 2010 Elsevier Ltd. All rights reserved.
PY - 2010/3/19
Y1 - 2010/3/19
N2 - An alpha-2,8-linked polysialic acid (polySia) capsule confers immune tolerance to neuroinvasive, pathogenic prokaryotes such as Escherichia coli K1 and Neisseria meningitidis and supports host infection by means of molecular mimicry. Bacteriophages of the K1 family, infecting E. coli K1, specifically recognize and degrade this polySia capsule utilizing tailspike endosialidases. While the crystal structure for the catalytic domain of the endosialidase of bacteriophage K1F (endoNF) has been solved, there is yet no structural information on the mode of polySia binding and cleavage available. The crystal structure of activity deficient active-site mutants of the homotrimeric endoNF cocrystallized with oligomeric sialic acid identified three independent polySia binding sites in each endoNF monomer. The bound oligomeric sialic acid displays distinct conformations at each site. In the active site, a Sia(3) molecule is bound in an extended conformation representing the enzyme-product complex. Structural and biochemical data supported by molecular modeling enable to propose a reaction mechanism for polySia cleavage by endoNF.
AB - An alpha-2,8-linked polysialic acid (polySia) capsule confers immune tolerance to neuroinvasive, pathogenic prokaryotes such as Escherichia coli K1 and Neisseria meningitidis and supports host infection by means of molecular mimicry. Bacteriophages of the K1 family, infecting E. coli K1, specifically recognize and degrade this polySia capsule utilizing tailspike endosialidases. While the crystal structure for the catalytic domain of the endosialidase of bacteriophage K1F (endoNF) has been solved, there is yet no structural information on the mode of polySia binding and cleavage available. The crystal structure of activity deficient active-site mutants of the homotrimeric endoNF cocrystallized with oligomeric sialic acid identified three independent polySia binding sites in each endoNF monomer. The bound oligomeric sialic acid displays distinct conformations at each site. In the active site, a Sia(3) molecule is bound in an extended conformation representing the enzyme-product complex. Structural and biochemical data supported by molecular modeling enable to propose a reaction mechanism for polySia cleavage by endoNF.
KW - Bacteriophages/enzymology
KW - Catalytic Domain
KW - Crystallography, X-Ray
KW - Glycoside Hydrolases
KW - Models, Molecular
KW - Mutant Proteins/chemistry
KW - Neuraminidase/chemistry
KW - Protein Structure, Secondary
KW - Sialic Acids/metabolism
KW - Substrate Specificity
KW - Viral Tail Proteins/chemistry
U2 - 10.1016/j.jmb.2010.01.028
DO - 10.1016/j.jmb.2010.01.028
M3 - SCORING: Journal article
C2 - 20096705
VL - 397
SP - 341
EP - 351
JO - J MOL BIOL
JF - J MOL BIOL
SN - 0022-2836
IS - 1
ER -