On the role of electrostatics in protein–protein interactions

Zhang, Zhe; Witham, Shawn; Alexov, Emil

doi:10.1088/1478-3975/8/3/035001

Cited by 148 publications

(130 citation statements)

References 147 publications

Supporting

Mentioning

118

Contrasting

Order By: Relevance

“…This interaction relies mainly on electrostatic forces. We found a series of ionic interactions within Ͻ10 Å, enough to generate a strong binding of the two molecules within such proximity (48).…”

Section: Discussionmentioning

confidence: 84%

Selective Acquisition of Host-Derived ICAM-1 by HIV-1 Is a Matrix-Dependent Process

Jalaguier

Cantin

Maaroufi

et al. 2015

J Virol

View full text Add to dashboard Cite

HIV-1 acquires an impressive number of foreign components during its formation. Despite all previous efforts spent studying the nature and functionality of virus-anchored host molecules, the exact mechanism(s) through which such constituents are acquired by HIV-1 is still unknown. However, in the case of ICAM-1, one of the most extensively studied transmembrane proteins found associated with mature virions, the Pr55Gag precursor polyprotein appears to be a potential interaction partner. We investigated and characterized at the molecular level the process of ICAM-1 incorporation using initially a Pr55Gag -based virus-like particle (VLP) model. Substitution of various domains of Pr55Gag , such as the nucleocapsid, SP2, or p6, had no effect on the acquisition of ICAM-1. We found that the structural matrix protein (MA) is mandatory for ICAM-1 incorporation within VLPs, and we confirmed this novel observation with the replication-competent HIV-1 molecular clone NL4.3. Additional studies suggest that the C-terminal two-thirds of MA, and especially 13 amino acids positioned inside the fifth ␣-helix, are important. Moreover, based on three-dimensional (3D) modeling of protein-protein interactions (i.e., protein-protein docking) and further validation by a virus capture assay, we found that a series of acidic residues in the MA domain interact with basic amino acids located in the ICAM-1 cytoplasmic tail. Our findings provide new insight into the molecular mechanism governing the acquisition of ICAM-1, a host molecule known to enhance HIV-1 infectivity in a significant manner. Altogether, these observations offer a new avenue for the development of antiviral therapeutics that are directed at a target of host origin. IMPORTANCEIntercellular adhesion molecule 1 (ICAM-1) is a cell surface host component known to be efficiently inserted within emerging HIV-1 particles. It has been demonstrated that host-derived ICAM-1 molecules act as a strong attachment factor and increase HIV-1 infectivity substantially. Despite previous efforts spent studying virus-associated host molecules, the precise mechanism(s) through which such constituents are inserted within emerging HIV-1 particles still remains obscure. Previous data suggest that the Pr55Gag precursor polyprotein appears as a potential interaction partner with ICAM-1. In the present study, we demonstrate that the HIV-1 matrix domain plays a key role in the ICAM-1 incorporation process. Some observations were confirmed with whole-virus preparations amplified in primary human cells, thereby providing physiological significance to our data.

show abstract

Section: Discussionmentioning

confidence: 84%

Selective Acquisition of Host-Derived ICAM-1 by HIV-1 Is a Matrix-Dependent Process

Jalaguier

Cantin

Maaroufi

et al. 2015

J Virol

View full text Add to dashboard Cite

show abstract

“…Taking into consideration the large number of different macromolecules in living cells, binding specificity plays an important role in recognizing unambiguous binding partners among an overabundance of other molecules [41, 42]. Binding specificity includes multiple factors such as concentrations and compartmentalization of the macromolecules, their shapes, charge and steric complementarity, conformational flexibility, the ability to recognize each other at relatively large distance (mainly through non-specific electrostatic interactions) and to form functioning complex by specific interactions within hot spots [41, 43]. …”

Section: Impact Of Mutations On Protein-protein Protein-ligand and Pmentioning

confidence: 99%

Structural and physico-chemical effects of disease and non-disease nsSNPs on proteins

Kucukkal

Petukh

et al. 2015

Current Opinion in Structural Biology

Self Cite

187

141

View full text Add to dashboard Cite

This review emphasizes the effects of naturally occurring mutations on structural features and physico-chemical properties of proteins. The basic protein characteristics considered are stability, dynamics, and the binding of proteins and methods for assessing effects of mutations on these macromolecular characteristics are briefly outlined. It is emphasized that the above entities mostly reflect global characteristics of considered macromolecules, while given mutations may alter the local structural features such as salt bridges and hydrogen bonds without affecting the global ones. Furthermore, it is pointed out that disease-causing mutations frequently involve a drastic change of amino acid physico-chemical properties such as charge, hydrophobicity, and geometry, and are less surface exposed than polymorphic mutations.

show abstract

“…The chemical potential or activity of protons, i.e. pH, is thus an important handle to control intermolecular electrostatic interactions in both biological and technical contexts [1]. Protons, however, may be in competition for binding sites with other ions and solutes in the solution.…”

Section: Introductionmentioning

confidence: 99%

Anisotropic protein–protein interactions due to ion binding

Lund

2016

Colloids and Surfaces B: Biointerfaces

View full text Add to dashboard Cite

On the role of electrostatics in protein–protein interactions

Cited by 148 publications

References 147 publications

Selective Acquisition of Host-Derived ICAM-1 by HIV-1 Is a Matrix-Dependent Process

Selective Acquisition of Host-Derived ICAM-1 by HIV-1 Is a Matrix-Dependent Process

Structural and physico-chemical effects of disease and non-disease nsSNPs on proteins

Anisotropic protein–protein interactions due to ion binding

Contact Info

Product

Resources

About