Amino acid motifs for the identification of novel protein interactants

Aloysius Wong; Chuyun Bi; Wei Chi; Ningxin Hu; Chris Gehring

doi:10.1016/j.csbj.2022.12.012

Amino acid motifs for the identification of novel protein interactants

Comput Struct Biotechnol J. 2022 Dec 10:21:326-334. doi: 10.1016/j.csbj.2022.12.012. eCollection 2023.

Authors

Aloysius Wong^{1

2

3}, Chuyun Bi^{1

2

3}, Wei Chi¹, Ningxin Hu¹, Chris Gehring⁴

Affiliations

¹ Department of Biology, College of Science and Technology, Wenzhou-Kean University, 88 Daxue Road, Ouhai, Wenzhou, Zhejiang Province 325060, China.
² Wenzhou Municipal Key Lab for Applied Biomedical and Biopharmaceutical Informatics, Ouhai, Wenzhou, Zhejiang Province 325060, China.
³ Zhejiang Bioinformatics International Science and Technology Cooperation Center, Ouhai, Wenzhou, Zhejiang Province 325060, China.
⁴ Department of Chemistry, Biology & Biotechnology, University of Perugia, Perugia 06121, Italy.

Abstract

Biological systems consist of multiple components of different physical and chemical properties that require complex and dynamic regulatory loops to function efficiently. The discovery of ever more novel interacting sites in complex proteins suggests that we are only beginning to understand how cellular and biological functions are integrated and tuned at the molecular and systems levels. Here we review recently discovered interacting sites which have been identified through rationally designed amino acid motifs diagnostic for specific molecular functions, including enzymatic activities and ligand-binding properties. We specifically discuss the nature of the latter using as examples, novel hormone recognition and gas sensing sites that occur in moonlighting protein complexes. Drawing evidence from the current literature, we discuss the potential implications at the cellular, tissue, and/or organismal levels of such non-catalytic interacting sites and provide several promising avenues for the expansion of amino acid motif searches to discover hitherto unknown protein interactants and interaction networks. We believe this knowledge will unearth unexpected functions in both new and well-characterized proteins, thus filling existing conceptual gaps or opening new avenues for applications either as drug targets or tools in pharmacology, cell biology and bio-catalysis. Beyond this, motif searches may also support the design of novel, effective and sustainable approaches to crop improvements and the development of new therapeutics.

Keywords: Amino acid motifs; Functional centers; Gas sensing; Hidden domains; Hormone perception; Moonlighting proteins; Protein interactants; Search motif; Sequence analysis.

Publication types

Review