Institut for Biomedicin

Thomas Vorup-Jensen

The role of nanometer-scaled ligand patterns in polyvalent binding by large mannan-binding lectin oligomers

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Standard

The role of nanometer-scaled ligand patterns in polyvalent binding by large mannan-binding lectin oligomers. / Gjelstrup, Louise C; Kaspersen, Jørn D; Behrens, Manja A; Pedersen, Jan S; Thiel, Steffen; Kingshott, Peter; Oliveira, Cristiano L P; Thielens, Nicole M; Vorup-Jensen, Thomas.

I: Journal of Immunology, Bind 188, Nr. 3, 01.02.2012, s. 1292-306.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Gjelstrup, LC, Kaspersen, JD, Behrens, MA, Pedersen, JS, Thiel, S, Kingshott, P, Oliveira, CLP, Thielens, NM & Vorup-Jensen, T 2012, 'The role of nanometer-scaled ligand patterns in polyvalent binding by large mannan-binding lectin oligomers', Journal of Immunology, bind 188, nr. 3, s. 1292-306. https://doi.org/10.4049/jimmunol.1103012

APA

CBE

Gjelstrup LC, Kaspersen JD, Behrens MA, Pedersen JS, Thiel S, Kingshott P, Oliveira CLP, Thielens NM, Vorup-Jensen T. 2012. The role of nanometer-scaled ligand patterns in polyvalent binding by large mannan-binding lectin oligomers. Journal of Immunology. 188(3):1292-306. https://doi.org/10.4049/jimmunol.1103012

MLA

Vancouver

Author

Gjelstrup, Louise C ; Kaspersen, Jørn D ; Behrens, Manja A ; Pedersen, Jan S ; Thiel, Steffen ; Kingshott, Peter ; Oliveira, Cristiano L P ; Thielens, Nicole M ; Vorup-Jensen, Thomas. / The role of nanometer-scaled ligand patterns in polyvalent binding by large mannan-binding lectin oligomers. I: Journal of Immunology. 2012 ; Bind 188, Nr. 3. s. 1292-306.

Bibtex

@article{28792af82c0c4d73b1721b9c8aff20c9,
title = "The role of nanometer-scaled ligand patterns in polyvalent binding by large mannan-binding lectin oligomers",
abstract = "Mannan-binding lectin (MBL) is an important protein of the innate immune system and protects the body against infection through opsonization and activation of the complement system on surfaces with an appropriate presentation of carbohydrate ligands. The quaternary structure of human MBL is built from oligomerization of structural units into polydisperse complexes typically with three to eight structural units, each containing three lectin domains. Insight into the connection between the structure and ligand-binding properties of these oligomers has been lacking. In this article, we present an analysis of the binding to neoglycoprotein-coated surfaces by size-fractionated human MBL oligomers studied with small-angle x-ray scattering and surface plasmon resonance spectroscopy. The MBL oligomers bound to these surfaces mainly in two modes, with dissociation constants in the micro to nanomolar order. The binding kinetics were markedly influenced by both the density of ligands and the number of ligand-binding domains in the oligomers. These findings demonstrated that the MBL-binding kinetics are critically dependent on structural characteristics on the nanometer scale, both with regard to the dimensions of the oligomer, as well as the ligand presentation on surfaces. Therefore, our work suggested that the surface binding of MBL involves recognition of patterns with dimensions on the order of 10-20 nm. The recent understanding that the surfaces of many microbes are organized with structural features on the nanometer scale suggests that these properties of MBL ligand recognition potentially constitute an important part of the pattern-recognition ability of these polyvalent oligomers.",
keywords = "Humans, Immunity, Innate, Kinetics, Ligands, Mannose-Binding Lectin, Nanostructures, Protein Binding, Protein Multimerization, Protein Structure, Quaternary",
author = "Gjelstrup, {Louise C} and Kaspersen, {J{\o}rn D} and Behrens, {Manja A} and Pedersen, {Jan S} and Steffen Thiel and Peter Kingshott and Oliveira, {Cristiano L P} and Thielens, {Nicole M} and Thomas Vorup-Jensen",
year = "2012",
month = "2",
day = "1",
doi = "10.4049/jimmunol.1103012",
language = "English",
volume = "188",
pages = "1292--306",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

RIS

TY - JOUR

T1 - The role of nanometer-scaled ligand patterns in polyvalent binding by large mannan-binding lectin oligomers

AU - Gjelstrup, Louise C

AU - Kaspersen, Jørn D

AU - Behrens, Manja A

AU - Pedersen, Jan S

AU - Thiel, Steffen

AU - Kingshott, Peter

AU - Oliveira, Cristiano L P

AU - Thielens, Nicole M

AU - Vorup-Jensen, Thomas

PY - 2012/2/1

Y1 - 2012/2/1

N2 - Mannan-binding lectin (MBL) is an important protein of the innate immune system and protects the body against infection through opsonization and activation of the complement system on surfaces with an appropriate presentation of carbohydrate ligands. The quaternary structure of human MBL is built from oligomerization of structural units into polydisperse complexes typically with three to eight structural units, each containing three lectin domains. Insight into the connection between the structure and ligand-binding properties of these oligomers has been lacking. In this article, we present an analysis of the binding to neoglycoprotein-coated surfaces by size-fractionated human MBL oligomers studied with small-angle x-ray scattering and surface plasmon resonance spectroscopy. The MBL oligomers bound to these surfaces mainly in two modes, with dissociation constants in the micro to nanomolar order. The binding kinetics were markedly influenced by both the density of ligands and the number of ligand-binding domains in the oligomers. These findings demonstrated that the MBL-binding kinetics are critically dependent on structural characteristics on the nanometer scale, both with regard to the dimensions of the oligomer, as well as the ligand presentation on surfaces. Therefore, our work suggested that the surface binding of MBL involves recognition of patterns with dimensions on the order of 10-20 nm. The recent understanding that the surfaces of many microbes are organized with structural features on the nanometer scale suggests that these properties of MBL ligand recognition potentially constitute an important part of the pattern-recognition ability of these polyvalent oligomers.

AB - Mannan-binding lectin (MBL) is an important protein of the innate immune system and protects the body against infection through opsonization and activation of the complement system on surfaces with an appropriate presentation of carbohydrate ligands. The quaternary structure of human MBL is built from oligomerization of structural units into polydisperse complexes typically with three to eight structural units, each containing three lectin domains. Insight into the connection between the structure and ligand-binding properties of these oligomers has been lacking. In this article, we present an analysis of the binding to neoglycoprotein-coated surfaces by size-fractionated human MBL oligomers studied with small-angle x-ray scattering and surface plasmon resonance spectroscopy. The MBL oligomers bound to these surfaces mainly in two modes, with dissociation constants in the micro to nanomolar order. The binding kinetics were markedly influenced by both the density of ligands and the number of ligand-binding domains in the oligomers. These findings demonstrated that the MBL-binding kinetics are critically dependent on structural characteristics on the nanometer scale, both with regard to the dimensions of the oligomer, as well as the ligand presentation on surfaces. Therefore, our work suggested that the surface binding of MBL involves recognition of patterns with dimensions on the order of 10-20 nm. The recent understanding that the surfaces of many microbes are organized with structural features on the nanometer scale suggests that these properties of MBL ligand recognition potentially constitute an important part of the pattern-recognition ability of these polyvalent oligomers.

KW - Humans

KW - Immunity, Innate

KW - Kinetics

KW - Ligands

KW - Mannose-Binding Lectin

KW - Nanostructures

KW - Protein Binding

KW - Protein Multimerization

KW - Protein Structure, Quaternary

U2 - 10.4049/jimmunol.1103012

DO - 10.4049/jimmunol.1103012

M3 - Journal article

C2 - 22219330

VL - 188

SP - 1292

EP - 1306

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -