α2-μ-Globulin Fragment (A2-f) from Kidneys of Male Rats forms Multimers in Vitro

Abstract

Abstract-2-µ-Globulin fragment (A2-f) functions as a fatty acid binding protein in kidneys of male rats. It has 100% sequence homology with amino acids 10-160 of 2-µ-Globulin (A2), an 18.6-kDa protein that is synthesized in male rat liver and is present in urine. A2-f is produced from A2 by the removal of 3 residues from the N-terminus and 9 amino acids residues from the C-terminus. This project aimed to isolate and purify A2-f (to >90% purity) for NMR analysis since the solution state structure of A2-f is still unknown. The purification failed due to formation of multimers in vitro but it did reveal heterogeneity of this protein as isolated from tissue.Index Terms-2--Globulin fragment (A2-f), 2--Globulin (A2), kidney fatty acid binding protein, Lipocalins, protein aggregation, male rat urinary proteins.

2-μ-Globulin Fragment: A Unique Protein in the Kidneys

“…α 2-μ-Globulin fragment (A 2 -f) represents about 5% of the total soluble protein content of the kidney [1,2]. It was initially thought to be a unique kidney fatty acid binding protein for several reasons: (a) it has a similar molecular size as all known FABPs, is found in the soluble protein fraction; and (b) it is abundant in cells with high fatty acid flux and binds long chain fatty acids in vitro [2,3].…”

“…It is believed that unusual structural features permit A 2 -f to be targeted to the proximal tubule cell, to escape lysosomal degradation and to enter the cytosol [4,5]. A study showed that A 2 is synthesized in the liver but not in the kidney.…”