Study Of Aggregation Of Beta-2-microglobulin And The Multifuntional Inhibitor Design

β2-microglobulin(β2m)is the light chain of human leukocyte antigen(HLA),which plays an important role in the structural stability and expression stability of HLA.It helps the HLA properly self-assemble and then present antigens to T-cells.The protein dissociates from the heavy chain of HLA and eventually metabolized by kidneys.Hemodialysis is an important means to sustain the life of patients with end-stage renal diseases.However,due to the failure to remove β2m,it accumulates continuously in the human body,and finally deposites in bones,joints and organs through the blood circulation to form amyloid aggregates,which leads to diseases known as dialysis-related amyloidosis(DRA).Thus,it is of great value to develop meterials able to capture β2m or to inhibite its aggregation at molecular level.Herein,we expressed and purified wild-type or eGFP fused β2m by E.coli system and explored its mechanism of aggregation.With the identified key fragment of β2m,we have designed a nanomaterial,which is composed of a single protein as the core,the outer package of thin polyme shell,and a β2m-binding peptide conjugated on the surface.By utilizing fluorescence kinetics,fluorescence co-localization imaging and cytotoxicity assays,we have confirmed that the nanomaterial could effectively inhibit the aggragation of β2m and capture it on the surface.In sum,based on the study of the aggregation mechanism of β2m,we have developed a multifunctional nanomaterial,which could be a poteintial drug for DRA,as well as a absorbing material during dialysis treatment.