Evolution and Mutations of Beta 2 Microglobulin

TL;DR

This paper investigates the evolution of beta-2 microglobulin's hydropathic shapes, revealing key evolutionary trends and mutation effects, with results aligning well with experimental data on sequence evolution and mutations.

Contribution

It introduces a hydrodynamic topological shape evolution method to analyze protein evolution and mutation impacts, providing new insights into beta-2 microglobulin's functional adaptations.

Findings

Excellent agreement with experimental data on mouse-human evolution

Identification of mutation D76N's role in amyloid aggregation

Analysis of six other DN test mutations

Abstract

Here we examine the evolution of beta-2 microglobulin in terms of its hydropathic shapes, a theoretical construct that has revealed important trends. The dynamics of many proteins are largely driven by interactions between the protein itself and the thin water film that covers it. \b{eta}2m constitutes the basic building unit of the immunoglobulin superfamily; the evolution of its amino acid sequences from chickens to mice to humans provides new information about its multiple functions. Our hydrodynamic method involves concepts of topological shape evolution towards a critical point for optimized functions. The results are in excellent agreement with experiment for the details of the mouse-human evolution, as well as both the dangerous natural amyloid aggregation mutation D76N, and six other DN test mutations.