The surface lipoprotein E (VlsE) of the Lyme disease spirochete bacterium

Introduction

The surface lipoprotein, , is responsible for the infectious properties of the Lyme disease spirochete, Borrelia burgdorferi^[1]. VlsE uses several immune evasive strategies, giving the disease its characteristically infectious behavior. Specifically, antigenic variation and suppression of innate and acquired immune response aid the disease in successful infection^[2]. Antigenic variation is an effective strategy in order to protect the vital structural properties of the spirochete. Expressed antigenic variation is produced by segmental gene conversion through variable regions of the lipoprotein^[3][4]. See also:
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VlsE of Borrelia
VlsE

Structure

Approximately 75% of the VlsE protein primary structure is invariable and highly conserved. There are N and C terminal regions of invariability, or direct repeats, which flank the cassette region where the invariable regions(IR) of the cassette reside^[5]. Within the cassette region exists silent cassettes that are unexpressed. The variable regions(VR) of VlsE ensure the survival of the invariable regions which hold the major structure and physiological function^[1]. By within the distal core of the protein, the variable regions serve as protection from the hosts immune system.

VlsE is made up of eleven alpha(α) helices, seven of which (α4-α10) reside in the core region of the distal portion of the protein ^[5]. These α-helices make up the cassette region of the protein, within which there are six variable regions and ^[1][5]. The six variable regions provide the variation necessary to evade the host immune system^[1] . Variability is produced via amino acid substitutions concentrated to a small portion of the variable region, which likely produces a conformational change of the epitope allowing it to elude the host immune system^[5].

Functionality

Although the exact function of the VlsE surface lipoprotein is unknown, three invariable regions have been found to show unique properties: IR2, IR4, and IR6 ^[1][5]. forms alpha helix 10, which is almost entirely buried within the center of the membrane distal regions encased by the variable regions, it has only 13.7% surface exposure^[5]. IR6 has an epitope which serves to increase the antibody affinity for binding, allowing it to distract the immune response from attacking more accessible sites ^[6]. While, were found to have significant antigenicity only in mice and at much lower rates when compared to IR6 ^[1]. By encasing these invariable regions within the distal core of the protein, the variable regions provide protection for the invariable regions from the host immune system.

Antigenic Variation

When mice were infected segments of silent cassettes recombine into the VlsE cassette region through an unknown gene conversion mechanism. The silent cassette region is inserted, but remains unaltered otherwise ^[1][3]. Antigenic variation in VlsE involves the vls locus of B. burgdorferi on the linear plasmid Ip 28-1^[3]. The locus contains both the expression site of the VlsE lipoprotein and 15 contiguous silent cassette region six. These silent cassettes are closely homologous to the central cassette regions; the only differences being from the six variable regions within each cassette. The variation usually begins 4 days after infection and continues throughout the course of the disease^[5]. In mice, four days post infection 50% of the population has at least one or more recombination events; after 28 days, no parental VlsE sequence is detected ^[7].