Evolution and Mutations of Beta 2 Microglobulin

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.