Biglycan is a small
leucine-rich repeat
A leucine-rich repeat (LRR) is a protein structural motif that forms an α/β horseshoe tertiary structure, fold. It is composed of repeating 20–30 amino acid stretches that are unusually rich in the hydrophobic amino acid leucine. These Pr ...
proteoglycan
Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a serine (Ser) residue to w ...
(SLRP) which is found in a variety of extracellular matrix tissues, including
bone
A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...
,
cartilage
Cartilage is a resilient and smooth type of connective tissue. Semi-transparent and non-porous, it is usually covered by a tough and fibrous membrane called perichondrium. In tetrapods, it covers and protects the ends of long bones at the joints ...
and
tendon
A tendon or sinew is a tough band of fibrous connective tissue, dense fibrous connective tissue that connects skeletal muscle, muscle to bone. It sends the mechanical forces of muscle contraction to the skeletal system, while withstanding tensi ...
. In humans, biglycan is encoded by the ''BGN''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
which is located on the
X chromosome
The X chromosome is one of the two sex chromosomes in many organisms, including mammals, and is found in both males and females. It is a part of the XY sex-determination system and XO sex-determination system. The X chromosome was named for its u ...
.
The name "biglycan" was proposed in an article by Fisher, Termine and Young in an article in the
Journal of Biological Chemistry
The ''Journal of Biological Chemistry'' (''JBC'') is a weekly peer-reviewed scientific journal that was established in 1905., jbc.org Since 1925, it is published by the American Society for Biochemistry and Molecular Biology. It covers research i ...
in 1989 because the
proteoglycan
Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a serine (Ser) residue to w ...
contained two GAG chains; formerly it was known as proteoglycan-I (PG-I).
Structure
Biglycan consists of a protein core containing leucine-rich repeat regions and two
glycosaminoglycan
Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case o ...
(GAG) chains consisting of either
chondroitin sulfate
Chondroitin sulfate is a sulfated glycosaminoglycan (GAG) composed of a chain of alternating sugars (N-Acetylgalactosamine, N-acetylgalactosamine and glucuronic acid). It is usually found attached to proteins as part of a proteoglycan. A chondroit ...
(CS) or
dermatan sulfate (DS), with DS being more abundant in most
connective tissue
Connective tissue is one of the four primary types of animal tissue, a group of cells that are similar in structure, along with epithelial tissue, muscle tissue, and nervous tissue. It develops mostly from the mesenchyme, derived from the mesod ...
s. The CS/DS chains are attached at amino acids 5 and 10 in human biglycan.
The composition of the GAG chains has been reported as varying according to tissue of origin. Non-glycanated forms of biglycan (no GAG chains) increase with age in human articular
cartilage
Cartilage is a resilient and smooth type of connective tissue. Semi-transparent and non-porous, it is usually covered by a tough and fibrous membrane called perichondrium. In tetrapods, it covers and protects the ends of long bones at the joints ...
.
The composition of GAG chains of biglycan and
decorin
Decorin is a protein that in humans is encoded by the ''DCN'' gene.
Decorin is a proteoglycan that is on average 90 - 140 kilodaltons (kDa) in molecular weight. It belongs to the small leucine-rich proteoglycan (SLRP) family and consists of a ...
originating from the same tissue has been reported to be similar.
The structure of biglycan core protein is highly conserved across species; over 90%
homology has been reported for rat, mouse, bovine and human biglycan core proteins.
Function
Biglycan is believed to play a role in the mineralization of bone.
Knock-out mice
A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "Gene knockout, knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They ...
that have had the gene for biglycan suppressed (Bgn -/-) have an
osteoporosis
Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk.
It is the most common reason f ...
-like
phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...
with reduced growth rate and lower
bone
A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...
mass than mice that can express biglycan.
Biglycan core protein binds to the
growth factors
A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regu ...
BMP-4 and influences its bioactivity.
It has also been reported that the presence of biglycan is necessary for
BMP-4 to exert its effects on
osteoblasts.
There is also evidence that biglycan binds to
TGF-beta 1.
Interactions
Biglycan interacts with
collagen
Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...
, both via the core protein and GAG chains.
It has been reported that biglycan interacts more strongly with
collagen type II than
collagen type I.
Biglycan has been reported to compete with
decorin
Decorin is a protein that in humans is encoded by the ''DCN'' gene.
Decorin is a proteoglycan that is on average 90 - 140 kilodaltons (kDa) in molecular weight. It belongs to the small leucine-rich proteoglycan (SLRP) family and consists of a ...
for the same binding site on
collagen
Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...
.
Biglycan has been shown to
interact with
SGCA.
Biglycan is a particularly important proteoglycan for binding to
lipoprotein
A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, sur ...
in human blood vessels, thus being a significant cause of
atherosclerosis
Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...
.
References
External links
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{{Proteoglycans
Proteoglycans
LRR proteins
Extracellular matrix proteins