Biomaterial Database

Dynamic of beta(2)-microglobulin fibril formation and reabsorption: the role of proteolysis. 2001

V Bellotti, and M Gallieni, and S Giorgetti, and D Brancaccio

Department of Biochemistry, University of Pavia, Pavia, Italy.

Dialysis-related amyloidosis (DRA) is caused by the deposition, in target tissues, of beta(2)-microglobulin (beta(2)M) in fibrillar conformation. Several reports indicate that fibrillar beta(2)M is chemically heterogeneous and such heterogeneity is partially related to the presence of truncated species of the protein. In association with the full-length species, a beta(2)M isoform lacking six N-terminal residues is present in all the samples of our collection of ex vivo fibrils. The pattern of proteolytic cleavage in amyloidosis and in other diseases is completely different, as demonstrated by the absence in fibrillar beta(2)M of the cleavage at lysine 58, which is contrary to that described in rheumatoid arthritis and other diseases. The role of limited proteolysis of beta(2)M in the pathogenesis of the disease is uncertain. However, we have shown that the apparently minor modification of the intact protein, such as the removal of N-terminal hexapeptide, is capable of dramatically affecting its stability, protection from proteolytic digestion, and enhance its capacity to make in vitro amyloid fibrils. The structure, folding dynamic, and function of the truncated species of beta(2)M, peculiar of DRA, could shed new light on the mechanism of beta(2)M fibril formation and reabsorption.

UI	MeSH Term	Description	Entries
D006435	Renal Dialysis	Therapy for the insufficient cleansing of the BLOOD by the kidneys based on dialysis and including hemodialysis, PERITONEAL DIALYSIS, and HEMODIAFILTRATION.	Dialysis, Extracorporeal,Dialysis, Renal,Extracorporeal Dialysis,Hemodialysis,Dialyses, Extracorporeal,Dialyses, Renal,Extracorporeal Dialyses,Hemodialyses,Renal Dialyses
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000042	Absorption	The physical or physiological processes by which substances, tissue, cells, etc. take up or take in other substances or energy.
D000682	Amyloid	A fibrous protein complex that consists of proteins folded into a specific cross beta-pleated sheet structure. This fibrillar structure has been found as an alternative folding pattern for a variety of functional proteins. Deposits of amyloid in the form of AMYLOID PLAQUES are associated with a variety of degenerative diseases. The amyloid structure has also been found in a number of functional proteins that are unrelated to disease.	Amyloid Fibril,Amyloid Fibrils,Amyloid Substance,Fibril, Amyloid,Fibrils, Amyloid,Substance, Amyloid
D000686	Amyloidosis	A group of sporadic, familial and/or inherited, degenerative, and infectious disease processes, linked by the common theme of abnormal protein folding and deposition of AMYLOID. As the amyloid deposits enlarge they displace normal tissue structures, causing disruption of function. Various signs and symptoms depend on the location and size of the deposits.	Amyloidoses
D001613	beta 2-Microglobulin	An 11-kDa protein associated with the outer membrane of many cells including LYMPHOCYTES. It is the small subunit of MHC CLASS I MOLECULES. Association with beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, CEREBROSPINAL FLUID, and urine of healthy individuals, and to a much greater degree in the urine and plasma of patients with tubular PROTEINURIA, renal failure, or kidney transplants.	Thymotaxin,beta 2 Microglobulin
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015394	Molecular Structure	The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.	Structure, Molecular,Molecular Structures,Structures, Molecular
D017510	Protein Folding	Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.	Protein Folding, Globular,Folding, Globular Protein,Folding, Protein,Foldings, Globular Protein,Foldings, Protein,Globular Protein Folding,Globular Protein Foldings,Protein Foldings,Protein Foldings, Globular