Cartilage proteoglycans. Structure and heterogeneity of the protein core and the effects of specific protein modifications on the binding to hyaluronate

Hardingham, Timothy E.; Ewins, R.J.F.; Muir, Helen

doi:10.1042/bj1570127

Cited by 204 publications

(108 citation statements)

References 37 publications

(53 reference statements)

Supporting

Mentioning

102

Contrasting

Order By: Relevance

“…Basic residues in link protein have been implicated in hyaluronate binding [35,36]. Two sets of these can be considered: (i) Arg9 is conserved in the PTRs of CD44 (Fig.…”

Section: Discussionmentioning

confidence: 99%

The protein fold of the hyaluronate‐binding proteoglycan tandem repeat domain of link protein, aggrecan and CD44 is similar to that of the C‐type lectin superfamily

Brissett

Perkins

1996

FEBS Letters

View full text Add to dashboard Cite

Link protein and aggrecan of the extracellular matrix each contain two proteoglycan tandem repeat (PTR) domains that interact with hyaluronate. Consensus secondary structure predictions for 59 PTR sequences and 129 C-type lectin sequences give similar patterns of two a-helices and up to seven ~strands. Protein fold recognition analyses show that the 59 PTR sequences are highly compatible with the C-type lectin crystal structure. The predicted fold consists of a conserved motif formed from an antiparaHel IS-sheet flanked by two s-helices, the motif being attached to two distinct types of ~-sheet region in the two superfamilies. Arg9 or Lysll on an exposed loop and up to three other Arg residues in the ~-sheet region are conserved and may form part of a hyaluronate binding site.

show abstract

“…Basic residues in link protein have been implicated in hyaluronate binding [35,36]. Two sets of these can be considered: (i) Arg9 is conserved in the PTRs of CD44 (Fig.…”

Section: Discussionmentioning

confidence: 99%

The protein fold of the hyaluronate‐binding proteoglycan tandem repeat domain of link protein, aggrecan and CD44 is similar to that of the C‐type lectin superfamily

Brissett

Perkins

1996

FEBS Letters

View full text Add to dashboard Cite

show abstract

“…Reduction/alkylation of proteoglycan was by treatment with 20 mM DTT followed by addition of iodoacetamide (Hardingham et al, 1976). The products of chondroitinase ABC digestion (Hascall and Heinegard, 1974), were separated by Sephacryl S-300 chromatography in PBS.…”

Section: Exogenous Macromoleculesmentioning

confidence: 99%

Hyaluronan receptor-directed assembly of chondrocyte pericellular matrix.

Knudson

1993

The Journal of Cell Biology

269

250

View full text Add to dashboard Cite

Abstract. Initial assembly of extracellular matrix occurs within a zone immediately adjacent to the chondrocyte cell surface termed the cell-associated or periceUular matrix. Assembly within the periceUular matrix compartment requires specific cell-matrix interactions to occur, that are mediated via membrane receptors. The focus of this study is to elucidate the mechanisms of assembly and retention of the cartilage pericellular matrix proteoglycan aggregates important for matrix organization. Assembly of newly synthesized chondrocyte pericellular matrices was inhibited by the addition to hyaluronan hexasaccharides, competitive inhibitors of the binding of hyaluronan to its cell surface receptor. Fully assembled chondrocyte pericellular matrices were displaced using hyaluronan hexasaccharides as well.When exogenous hyaluronan was added to matrixfree chondrocytes in combination with aggrecan, a pericellular matrix equivalent in size to an endogenous matrix formed within 30 min of incubation. Addition of hyaluronan and aggrecan to glutaraldehyde-fixed chondrocytes resulted in matrix assembly comparable to live chondrocytes. These matrices could be inhibited from assembling by the addition of excess hyaluronan hexasaccharides or displaced once assembled by subsequent incubation with hyaluronan hexasaccharides. The results indicate that the aggrecanrich chondrocyte pericellular matrix is not only on a scaffolding of hyaluronan, but actually anchored to the cell surface via the interaction between hyaluronan and hyaluronan receptors.

show abstract

“…Basic residues constitute the basis for link protein-hyaluronate interactions via the PTR domains [47,48], even though proteincarbohydrate interactions might be mediated also by hydrogen bond and hydrophobic contacts [49]. First, electrostatic surface potentials were calculated for mannose-binding protein and Eselectin as a control.…”

Section: Electrostatic Surface Calculations Of the G3 Crd And Scr Dommentioning

confidence: 99%

Conserved basic residues in the C-type lectin and short complement repeat domains of the G3 region of proteoglycans

Brissett

Perkins

1998

Biochemical Journal

View full text Add to dashboard Cite

Aggrecan is the major proteoglycan of the extracellular matrix in cartilage. It contains two N-terminal globular regions, G1 and G2, and one C-terminal globular region, G3. G3 is implicated in the intracellular processing of aggrecan and contains a C-type lectin carbohydrate recognition domain (CRD), frequent occurrences of a C-terminal short complement repeat (SCR) domain, and occasionally an N-terminal epidermal growth factor domain. The CRD and SCR domains in 13 G3 sequences were each subjected to structural analysis. Alignment of 131 sequences from all seven groups in the CRD superfamily defined a consensus length of 136 residues, in which 32% of residues were conserved. Although the G3 CRD sequences agreed with this consensus, they also contained five fully conserved basic residues that are atypical of the CRD superfamily. Homology modelling showed that four of these residues are located on a surface region on the CRD that is separate from the Ca2+-binding residues involved in carbohydrate interactions. One conserved basic residue is identical in position with that of a conserved basic residue that mediates hyaluronate binding in the structurally related proteoglycan tandem repeat (PTR) domain in G1 and in link protein. The alignment of 13 G3 SCR sequences with 101 sequences in the SCR superfamily showed good agreement with conserved residues in the SCR superfamily. There are also five conserved basic residues in the G3 SCR that are atypical of the SCR superfamily, and homology modelling showed that all five were located on one surface of the SCR. It is concluded that both the CRD and SCR domains in G3 possess basic residues that are atypical of their superfamilies and might be related to function, and that the G3 CRD domain shows an evolutionary relationship to the PTR domain in G1.

show abstract

Cartilage proteoglycans. Structure and heterogeneity of the protein core and the effects of specific protein modifications on the binding to hyaluronate

Cited by 204 publications

References 37 publications

The protein fold of the hyaluronate‐binding proteoglycan tandem repeat domain of link protein, aggrecan and CD44 is similar to that of the C‐type lectin superfamily

The protein fold of the hyaluronate‐binding proteoglycan tandem repeat domain of link protein, aggrecan and CD44 is similar to that of the C‐type lectin superfamily

Hyaluronan receptor-directed assembly of chondrocyte pericellular matrix.

Conserved basic residues in the C-type lectin and short complement repeat domains of the G3 region of proteoglycans

Contact Info

Product

Resources

About