Backbone and nearly complete side-chain chemical shift assignments reveal the human uncharacterized protein CXorf51A as intrinsically disordered

Christoph Wiedemann,Jan Jirschitzka,Kingsley Benjamin Obika,Frank Bordusa,Oliver Ohlenschlãger,Sandra Liebscher

doi:10.1007/s12104-021-10043-6

Abstract

Even though the human genome project showed that our DNA contains a mere 20,000 to 25,000 protein coding genes, an unexpectedly large number of these proteins remain functionally uncharacterized. A structural characterization of these “unknown” proteins may help to identify possible cellular tasks. We therefore used a combination of bioinformatics and nuclear magnetic resonance spectroscopy to structurally de-orphanize one of these gene products, the 108 amino acid human uncharacterized protein CXorf51A. Both our bioinformatics analysis as well as the ^1H, ^{13}C, ^{15}N backbone and near-complete side-chain chemical shift assignments indicate that it is an intrinsically disordered protein.

Highlights

Of the 156,460 protein entries in the Protein Data Bank (PDB), roughly 7700 distinct proteins or parts of proteins are of human origin (June 2021)
In addition to focused attempts by individual laboratories centered on single proteins, consortia using high-throughput approaches that combine multiple techniques and screen large protein libraries (e.g. RIKEN Structural Genomics/ Proteomics Initiative, Midwest Center for Structural Genomics, Structural Genomics Consortium) have emerged as effective forerunners in trying to determine every protein structure possible
In order to de-orphanize structural and functional uncharacterized human proteins, we report the nearly complete backbone and side-chain chemical shift assignments of CX05A and provide a chemical-shift-based secondary structure prediction

Summary

Introduction

Of the 156,460 protein entries in the Protein Data Bank (PDB), roughly 7700 distinct proteins or parts of proteins are of human origin (June 2021). Keywords Nuclear magnetic resonance spectroscopy · NMR · Intrinsically disordered protein · IDP · Human protein · Resonance chemical shift assignment · Structural and functional · Uncharacterized human protein Germany large knowledge gap between the number of human proteins and the available structural and detailed functional data.

Results

Conclusion