By the same authors

From the same journal

Structure of the Ultra-High-Affinity Colicin E2 DNase-Im2 Complex

Research output: Contribution to journalArticlepeer-review

Published copy (DOI)

Author(s)

Department/unit(s)

Publication details

JournalJournal of Molecular Biology
DatePublished - 16 Mar 2012
Issue number1-2
Volume417
Number of pages16
Pages (from-to)79-94
Original languageEnglish

Abstract

How proteins achieve high-affinity binding to a specific protein partner while simultaneously excluding all others is a major biological problem that has important implications for protein design. We report the crystal structure of the ultra-high-affinity protein-protein complex between the endonuclease domain of colicin E2 and its cognate immunity (Im) protein, Im2 (K(d)∼10(-)(15) M), which, by comparison to previous structural and biophysical data, provides unprecedented insight into how high affinity and selectivity are achieved in this model family of protein complexes. Our study pinpoints the role of structured water molecules in conjoining hotspot residues that govern stability with residues that control selectivity. A key finding is that a single residue, which in a noncognate context massively destabilizes the complex through frustration, does not participate in specificity directly but rather acts as an organizing center for a multitude of specificity interactions across the interface, many of which are water mediated.

Discover related content

Find related publications, people, projects, datasets and more using interactive charts.

View graph of relations