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Vitronectin binds to the head region of Moraxella catarrhalis ubiquitous surface protein A2 and confers complement-inhibitory activity.

Singh, Birendra LU ; Blom, Anna LU ; Ünal, Can LU ; Nilson, Bo LU ; Mörgelin, Matthias LU and Riesbeck, Kristian LU (2010) In Molecular Microbiology 75. p.1426-1444
Abstract
Summary The serum resistance of the common respiratory pathogen Moraxella catarrhalis is mainly dependent on ubiquitous surface proteins (Usp) A1 and A2 that interact with complement factor 3 (C3) and complement inhibitor C4b binding protein (C4BP) preventing the alternative and classical pathways of the complement system respectively. UspA2 also has the capacity to attract vitronectin that in turn binds C9 and hereby inhibits membrane attack complex (MAC) formation. We found UspA2 as a major vitronectin binding protein and hence the UspA2/vitronectin interaction was studied in detail. The affinity constant (K(D)) for vitronectin binding to UspA2 was 2.3 x 10(-8) M, and the N-terminal region encompassing residues UspA2 30-170 bound... (More)
Summary The serum resistance of the common respiratory pathogen Moraxella catarrhalis is mainly dependent on ubiquitous surface proteins (Usp) A1 and A2 that interact with complement factor 3 (C3) and complement inhibitor C4b binding protein (C4BP) preventing the alternative and classical pathways of the complement system respectively. UspA2 also has the capacity to attract vitronectin that in turn binds C9 and hereby inhibits membrane attack complex (MAC) formation. We found UspA2 as a major vitronectin binding protein and hence the UspA2/vitronectin interaction was studied in detail. The affinity constant (K(D)) for vitronectin binding to UspA2 was 2.3 x 10(-8) M, and the N-terminal region encompassing residues UspA2 30-170 bound vitronectin with a K(D) of 7.9 x 10(-8) M. Electron microscopy verified that the active binding domain (UspA2(30-177)) was located at the head region of UspA2. Experiments with recombinantly expressed vitronectin also revealed that UspA2(30-177) bound to the C-terminal region of vitronectin residues 312-396. Finally, when human serum was pre-incubated with UspA2, bacteria showed significantly less serum resistance. Our study directly reveals the binding mode between the N-terminal domain of UspA2 and the C-terminal part of vitronectin and thus sheds light upon the mechanism of M. catarrhalis-dependent serum resistance. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Microbiology
volume
75
pages
1426 - 1444
publisher
Wiley-Blackwell
external identifiers
  • wos:000275396200008
  • pmid:20199596
  • scopus:77949396489
ISSN
1365-2958
DOI
10.1111/j.1365-2958.2010.07066.x
language
English
LU publication?
yes
id
3d09c96b-16dc-4e5f-922b-4ce2f9d4659f (old id 1582582)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20199596?dopt=Abstract
date added to LUP
2010-04-08 08:34:48
date last changed
2018-05-29 11:28:50
@article{3d09c96b-16dc-4e5f-922b-4ce2f9d4659f,
  abstract     = {Summary The serum resistance of the common respiratory pathogen Moraxella catarrhalis is mainly dependent on ubiquitous surface proteins (Usp) A1 and A2 that interact with complement factor 3 (C3) and complement inhibitor C4b binding protein (C4BP) preventing the alternative and classical pathways of the complement system respectively. UspA2 also has the capacity to attract vitronectin that in turn binds C9 and hereby inhibits membrane attack complex (MAC) formation. We found UspA2 as a major vitronectin binding protein and hence the UspA2/vitronectin interaction was studied in detail. The affinity constant (K(D)) for vitronectin binding to UspA2 was 2.3 x 10(-8) M, and the N-terminal region encompassing residues UspA2 30-170 bound vitronectin with a K(D) of 7.9 x 10(-8) M. Electron microscopy verified that the active binding domain (UspA2(30-177)) was located at the head region of UspA2. Experiments with recombinantly expressed vitronectin also revealed that UspA2(30-177) bound to the C-terminal region of vitronectin residues 312-396. Finally, when human serum was pre-incubated with UspA2, bacteria showed significantly less serum resistance. Our study directly reveals the binding mode between the N-terminal domain of UspA2 and the C-terminal part of vitronectin and thus sheds light upon the mechanism of M. catarrhalis-dependent serum resistance.},
  author       = {Singh, Birendra and Blom, Anna and Ünal, Can and Nilson, Bo and Mörgelin, Matthias and Riesbeck, Kristian},
  issn         = {1365-2958},
  language     = {eng},
  pages        = {1426--1444},
  publisher    = {Wiley-Blackwell},
  series       = {Molecular Microbiology},
  title        = {Vitronectin binds to the head region of Moraxella catarrhalis ubiquitous surface protein A2 and confers complement-inhibitory activity.},
  url          = {http://dx.doi.org/10.1111/j.1365-2958.2010.07066.x},
  volume       = {75},
  year         = {2010},
}