Novel functions and binding mechanisms of carbohydrate-binding proteins determined by force measurements

Research output: Contribution to journalArticle

Abstract

Cell surface carbohydrates are important targets for many cell surface receptors, and they mediate crucial biological processes ranging from pathogen infectivity to neutrophil adhesion to drug targeting. A central challenge is to identify relationships between lectin architecture and function that influence the adhesion strength, avidity, and kinetics of receptor-glycan bonds. This information is central both to understanding recognition mechanisms and to developing effective therapeutic agents for drug targeting or for preventing infection. Increasingly, force probes are used to assess structure activity relationships of both the glycan ligands and the receptors that bind them, as well as molecular mechanisms underlying binding and adhesion. This review describes recent advances in the use of different force measurement techniques to quantify receptor-glycan bond parameters, and to identify novel features of molecular mechanisms underlying recognition and adhesion. The examples discussed focus in particular on single bond rupture, surface force measurements, and micropipette manipulation. This review emphasizes the often-unique information obtained from studies of lectin interactions with carbohydrate ligands that complement more common structure determinations and solution binding studies.

Original languageEnglish (US)
Pages (from-to)743-759
Number of pages17
JournalCurrent Protein and Peptide Science
Volume12
Issue number8
DOIs
StatePublished - Dec 1 2011

Fingerprint

Force measurement
Polysaccharides
Adhesion
Drug Delivery Systems
Lectins
Carbohydrates
Ligands
Biological Phenomena
Surface measurement
Bond strength (materials)
Cell Surface Receptors
Pathogens
Structure-Activity Relationship
Rupture
Neutrophils
Kinetics
Infection
saccharide-binding proteins
Therapeutics

Keywords

  • Adhesin
  • Atomic force microscopy
  • Binding kinetics
  • Catch bond
  • Force measurements
  • Lectin
  • Surface force apparatus

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

@article{e09f1bd45ba54e1bb2fb22ab861f1d1c,
title = "Novel functions and binding mechanisms of carbohydrate-binding proteins determined by force measurements",
abstract = "Cell surface carbohydrates are important targets for many cell surface receptors, and they mediate crucial biological processes ranging from pathogen infectivity to neutrophil adhesion to drug targeting. A central challenge is to identify relationships between lectin architecture and function that influence the adhesion strength, avidity, and kinetics of receptor-glycan bonds. This information is central both to understanding recognition mechanisms and to developing effective therapeutic agents for drug targeting or for preventing infection. Increasingly, force probes are used to assess structure activity relationships of both the glycan ligands and the receptors that bind them, as well as molecular mechanisms underlying binding and adhesion. This review describes recent advances in the use of different force measurement techniques to quantify receptor-glycan bond parameters, and to identify novel features of molecular mechanisms underlying recognition and adhesion. The examples discussed focus in particular on single bond rupture, surface force measurements, and micropipette manipulation. This review emphasizes the often-unique information obtained from studies of lectin interactions with carbohydrate ligands that complement more common structure determinations and solution binding studies.",
keywords = "Adhesin, Atomic force microscopy, Binding kinetics, Catch bond, Force measurements, Lectin, Surface force apparatus",
author = "Leckband, {Deborah E.}",
year = "2011",
month = "12",
day = "1",
doi = "10.2174/138920311798841735",
language = "English (US)",
volume = "12",
pages = "743--759",
journal = "Current Protein and Peptide Science",
issn = "1389-2037",
publisher = "Bentham Science Publishers B.V.",
number = "8",

}

TY - JOUR

T1 - Novel functions and binding mechanisms of carbohydrate-binding proteins determined by force measurements

AU - Leckband, Deborah E.

PY - 2011/12/1

Y1 - 2011/12/1

N2 - Cell surface carbohydrates are important targets for many cell surface receptors, and they mediate crucial biological processes ranging from pathogen infectivity to neutrophil adhesion to drug targeting. A central challenge is to identify relationships between lectin architecture and function that influence the adhesion strength, avidity, and kinetics of receptor-glycan bonds. This information is central both to understanding recognition mechanisms and to developing effective therapeutic agents for drug targeting or for preventing infection. Increasingly, force probes are used to assess structure activity relationships of both the glycan ligands and the receptors that bind them, as well as molecular mechanisms underlying binding and adhesion. This review describes recent advances in the use of different force measurement techniques to quantify receptor-glycan bond parameters, and to identify novel features of molecular mechanisms underlying recognition and adhesion. The examples discussed focus in particular on single bond rupture, surface force measurements, and micropipette manipulation. This review emphasizes the often-unique information obtained from studies of lectin interactions with carbohydrate ligands that complement more common structure determinations and solution binding studies.

AB - Cell surface carbohydrates are important targets for many cell surface receptors, and they mediate crucial biological processes ranging from pathogen infectivity to neutrophil adhesion to drug targeting. A central challenge is to identify relationships between lectin architecture and function that influence the adhesion strength, avidity, and kinetics of receptor-glycan bonds. This information is central both to understanding recognition mechanisms and to developing effective therapeutic agents for drug targeting or for preventing infection. Increasingly, force probes are used to assess structure activity relationships of both the glycan ligands and the receptors that bind them, as well as molecular mechanisms underlying binding and adhesion. This review describes recent advances in the use of different force measurement techniques to quantify receptor-glycan bond parameters, and to identify novel features of molecular mechanisms underlying recognition and adhesion. The examples discussed focus in particular on single bond rupture, surface force measurements, and micropipette manipulation. This review emphasizes the often-unique information obtained from studies of lectin interactions with carbohydrate ligands that complement more common structure determinations and solution binding studies.

KW - Adhesin

KW - Atomic force microscopy

KW - Binding kinetics

KW - Catch bond

KW - Force measurements

KW - Lectin

KW - Surface force apparatus

UR - http://www.scopus.com/inward/record.url?scp=84857130097&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84857130097&partnerID=8YFLogxK

U2 - 10.2174/138920311798841735

DO - 10.2174/138920311798841735

M3 - Article

C2 - 22044144

AN - SCOPUS:84857130097

VL - 12

SP - 743

EP - 759

JO - Current Protein and Peptide Science

JF - Current Protein and Peptide Science

SN - 1389-2037

IS - 8

ER -