Towards a structural and functional analysis of the immunoglobulin-fold proteome.

Abstract

The immunoglobulinfold (Igfold) domain is a super-secondary structural motif consisting of a sandwich with two layers of β-sheets that is present in many proteins with very diverse biological functions covering a wide range of physiological processes. This domain presents a modular architecture built with β strands connected by variable length loops that has a highly conserved structural core of four β-strands and quite variable β-sheet extensions in the two sandwich layers that enable both divergent and convergent evolutionary mechanisms in the known Igfold proteome. The central role of this Igfold's structural plasticity in the evolutionary success of antibodies in our immune system is well established. Nature has also utilized this Igfold in all domains of life in many different physiological contexts that go way beyond the immune system. Here we will present a structural and functional overview of the utilization of the Igfold in different biological processes and in different cellular contexts to highlight some of the innumerable ways that this structural motif can interact in multidomain proteins to enable their diversity of functions. This includes shareable specific protein structure visualizations behind those functions that serve as starting points for further explorations of the biomolecular interactions spanning the Igfold proteome. This overview also highlights how this Igfold is being utilized through natural adaptation, engineering, and even building from scratch for a range of biotechnological applications.