Albumin domain mutants with enhanced Aβ binding capacity identified by phage display analysis for application in various peripheral Aβ elimination approaches of Alzheimer's disease treatment.

07:00 EST 3rd December 2019 | BioPortfolio

Summary of "Albumin domain mutants with enhanced Aβ binding capacity identified by phage display analysis for application in various peripheral Aβ elimination approaches of Alzheimer's disease treatment."

Deposition of amyloid protein, particularly Aβ , is a major contributor to the onset of Alzheimer's disease (AD). However, almost no deposition of Aβ in the peripheral tissues could be found. Human serum albumin (HSA), the most abundant protein in the blood, has been reported to inhibit amyloid formation through binding Aβ, which is believed to play an important role in the peripheral clearance of Aβ. We identified the Aβ binding site on HSA and developed HSA mutants with high binding capacities for Aβ using a phage display method. HSA fragment 187-385 (Domain II) was found to exhibit the highest binding capacity for Aβ compared with the other two HSA fragments. To elucidate the sequence that forms the binding site for Aβ on Domain II, a random screening of Domain II display phage biopanning was constructed. A number of mutants with higher Aβ binding capacities than the wild type were identified. These mutants exhibited stronger scavenging abilities than the wild type, as revealed via in vitro equilibrium dialysis of Aβ experiments. These findings provide useful basic data for developing a safer alternative therapy than Aβ vaccines and for application in plasma exchange as well as extracorporeal dialysis.


Journal Details

This article was published in the following journal.

Name: IUBMB life
ISSN: 1521-6551


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Medical and Biotech [MESH] Definitions

A family of transcription factors characterized by the presence of a bipartite DNA-binding domain known as the POU domain. The POU domain contains two subdomains, a POU-specific domain and a POU-homeodomain. The POU domain was originally identified as a region of approximately 150 amino acids shared between the Pit-1, Oct-1, Oct-2, and Unc-86 transcription factors.

A condition in which albumin level in blood (SERUM ALBUMIN) is below the normal range. Hypoalbuminemia may be due to decreased hepatic albumin synthesis, increased albumin catabolism, altered albumin distribution, or albumin loss through the urine (ALBUMINURIA).

A class of proteins that were originally identified by their ability to bind the DNA sequence CCAAT. The typical CCAAT-enhancer binding protein forms dimers and consists of an activation domain, a DNA-binding basic region, and a leucine-rich dimerization domain (LEUCINE ZIPPERS). CCAAT-BINDING FACTOR is structurally distinct type of CCAAT-enhancer binding protein consisting of a trimer of three different subunits.

DNA-binding domains present in proteins of the HMG-box superfamily including the archetypal HMGB PROTEINS, a number of sequence specific TRANSCRIPTION FACTORS, and other DNA-BINDING PROTEINS. The domains consist of 70-80 amino acids that form an L-shaped fold from three alpha-helical segments. The domain has the capacity to recognize and/or induce specific DNA structures and effect the accessibility of the DNA to other proteins involved in transcription, recombination, or DNA repair. (Note that not all HIGH MOBILITY GROUP PROTEINS contain this domain.)

A protein domain of about 70 amino acids in length that folds into a sandwich structure consisting of a beta sheet, alpha helix, and C-terminal hairpin loop which forms a hydrophobic methylated-DNA binding patch. It binds to methylated CPG ISLANDS in eukaryotes and occurs with other DNA and CHROMATIN binding domains such as AT-HOOK MOTIFS in eukaryotic DNA BINDING PROTEINS.

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