LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

Modulating binding affinity, specificity and configurations by multivalent interactions.

Photo from wikipedia

Biological functions of proteins rely on their specific interactions with binding partners. Many proteins contain multiple domains, which can bind to their targets that often have more than one binding… Click to show full abstract

Biological functions of proteins rely on their specific interactions with binding partners. Many proteins contain multiple domains, which can bind to their targets that often have more than one binding site, resulting in multivalent interactions. While it has been shown that multivalent interactions play an crucial role in modulating binding affinity and specificity, other potential effects of multivalent interactions are less explored. Here, we developed a broadly applicable transfer matrix formalism and used it to investigate the binding of two-domain ligands to targets with multiple binding sites. We show that 1) ligands with two specific binding domains can drastically boost both the binding affinity and specificity and down-shift the working concentration range, compared to single-domain ligands, 2) the presence of a positive domain-domain cooperativity or containing a non-specific binding domain can down-shift the working concentration range of ligands by increasing the binding affinity without compromising the binding specificity, 3) the configuration of the bound ligands has a strong concentration dependence, providing important insights into the physical origin of phase-separation processes taking place in living cells. In line with previous studies, our results suggest that multivalent interactions are utilized by cells for highly efficient regulation of target binding involved in a diverse range of cellular processes such as signal transduction, gene transcription, antibody-antigen recognition.

Keywords: domain; binding affinity; multivalent interactions; affinity specificity

Journal Title: Biophysical journal
Year Published: 2022

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.