The propagation of binding interactions to remote sites in proteins: Analysis of the binding of the monoclonal antibody D1.3 to lysozyme

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Abstract

The interaction of a ligand with a protein occurs at a local site (the binding site) and involves only a few residues; however, the effects of that interaction are often propagated to remote locations. The chain of events initiated by binding provides the basis for fundamental biological phenomena such as allosterism, signal transduction, and structural-stability modification. In this paper, a structure-based statistical thermodynamic approach is presented and used to predict the propagation of the stabilization effects triggered by the binding of the monoclonal antibody D1.3 to hen egg white lysozyme. Previously, Williams et al. [Williams, D.C., Benjamin, D.C., Poljak R. J. and Rule, G. S. (1996) J. Mol. Biol. 257, 866- 876] showed that the binding of this antibody affects the stability of hen egg white lysozyme and that the binding effects propagate to a selected number of residues at remote locations from the binding epitope. In this paper, we show that this phenomenon can be predicted from structure. The formalism presented here permits the identification of the structural path followed by cooperative interactions that originate at the binding site. It is shown that an important condition for the propagation of binding effects to distal regions is the presence of a significant fraction of residues with low structural stability in the uncomplexed binding site. A survey of protein structures indicates that many binding sites have a dual character and are defined by regions of high and low structural stabilities. The low-stability regions might be involved in the transmission of binding information to other regions in the protein.

Original languageEnglish (US)
Pages (from-to)10118-10122
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number18
DOIs
StatePublished - Aug 31 1999

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Muramidase
Protein Binding
Binding Sites
Egg White
Biological Phenomena
Proteins
Thermodynamics
Epitopes
Signal Transduction
Ligands
IgG D1.3
Antibodies
hen egg lysozyme

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

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abstract = "The interaction of a ligand with a protein occurs at a local site (the binding site) and involves only a few residues; however, the effects of that interaction are often propagated to remote locations. The chain of events initiated by binding provides the basis for fundamental biological phenomena such as allosterism, signal transduction, and structural-stability modification. In this paper, a structure-based statistical thermodynamic approach is presented and used to predict the propagation of the stabilization effects triggered by the binding of the monoclonal antibody D1.3 to hen egg white lysozyme. Previously, Williams et al. [Williams, D.C., Benjamin, D.C., Poljak R. J. and Rule, G. S. (1996) J. Mol. Biol. 257, 866- 876] showed that the binding of this antibody affects the stability of hen egg white lysozyme and that the binding effects propagate to a selected number of residues at remote locations from the binding epitope. In this paper, we show that this phenomenon can be predicted from structure. The formalism presented here permits the identification of the structural path followed by cooperative interactions that originate at the binding site. It is shown that an important condition for the propagation of binding effects to distal regions is the presence of a significant fraction of residues with low structural stability in the uncomplexed binding site. A survey of protein structures indicates that many binding sites have a dual character and are defined by regions of high and low structural stabilities. The low-stability regions might be involved in the transmission of binding information to other regions in the protein.",
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T1 - The propagation of binding interactions to remote sites in proteins

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N2 - The interaction of a ligand with a protein occurs at a local site (the binding site) and involves only a few residues; however, the effects of that interaction are often propagated to remote locations. The chain of events initiated by binding provides the basis for fundamental biological phenomena such as allosterism, signal transduction, and structural-stability modification. In this paper, a structure-based statistical thermodynamic approach is presented and used to predict the propagation of the stabilization effects triggered by the binding of the monoclonal antibody D1.3 to hen egg white lysozyme. Previously, Williams et al. [Williams, D.C., Benjamin, D.C., Poljak R. J. and Rule, G. S. (1996) J. Mol. Biol. 257, 866- 876] showed that the binding of this antibody affects the stability of hen egg white lysozyme and that the binding effects propagate to a selected number of residues at remote locations from the binding epitope. In this paper, we show that this phenomenon can be predicted from structure. The formalism presented here permits the identification of the structural path followed by cooperative interactions that originate at the binding site. It is shown that an important condition for the propagation of binding effects to distal regions is the presence of a significant fraction of residues with low structural stability in the uncomplexed binding site. A survey of protein structures indicates that many binding sites have a dual character and are defined by regions of high and low structural stabilities. The low-stability regions might be involved in the transmission of binding information to other regions in the protein.

AB - The interaction of a ligand with a protein occurs at a local site (the binding site) and involves only a few residues; however, the effects of that interaction are often propagated to remote locations. The chain of events initiated by binding provides the basis for fundamental biological phenomena such as allosterism, signal transduction, and structural-stability modification. In this paper, a structure-based statistical thermodynamic approach is presented and used to predict the propagation of the stabilization effects triggered by the binding of the monoclonal antibody D1.3 to hen egg white lysozyme. Previously, Williams et al. [Williams, D.C., Benjamin, D.C., Poljak R. J. and Rule, G. S. (1996) J. Mol. Biol. 257, 866- 876] showed that the binding of this antibody affects the stability of hen egg white lysozyme and that the binding effects propagate to a selected number of residues at remote locations from the binding epitope. In this paper, we show that this phenomenon can be predicted from structure. The formalism presented here permits the identification of the structural path followed by cooperative interactions that originate at the binding site. It is shown that an important condition for the propagation of binding effects to distal regions is the presence of a significant fraction of residues with low structural stability in the uncomplexed binding site. A survey of protein structures indicates that many binding sites have a dual character and are defined by regions of high and low structural stabilities. The low-stability regions might be involved in the transmission of binding information to other regions in the protein.

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