Consensus design of a NOD receptor leucine rich repeat domain with binding affinity for a muramyl dipeptide, a bacterial cell wall fragment. (17th April 2014)

• Record Type: Journal Article
• Authors: Parker, Rachael; Mercedes‐Camacho, Ana; Grove, Tijana Z.
• Is Part Of: Protein science. Volume 23:Number 6(2014:Jun.)
• Page Start: 790
• Page End: 800
• Publication Date: 2014-04-17
• Subjects: Proteins -- Periodicals; 572.6
• DOI: 10.1002/pro.2461
• Languages: English
• ISSNs: 0961-8368

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>Repeat proteins have recently emerged as especially well‐suited alternative binding scaffolds due to their modular architecture and biophysical properties. Here we present the design of a scaffold based on the consensus sequence of the leucine rich repeat (LRR) domain of the NOD family of cytoplasmic innate immune system receptors. Consensus sequence design has emerged as a protein design tool to create <italic>de novo</italic> proteins that capture sequence‐structure relationships and interactions present in nature. The multiple sequence alignment of 311 individual LRRs, which are the putative ligand‐recognition domain in NOD proteins, resulted in a consensus sequence protein containing two internal and N‐ and C‐capping repeats named CLRR2. CLRR2 protein is a stable, monomeric, and cysteine free scaffold that without any affinity maturation displays micromolar binding to muramyl dipeptide, a bacterial cell wall fragment. To our knowledge, this is the first report of direct interaction of a NOD LRR with a physiologically relevant ligand.</p> </abstract>