# STRUCTURE AND FUNCTION IN CARTILAGE LINK PROTEIN

> **NIH NIH R01** · UNIVERSITY OF SOUTH FLORIDA · 1993 · $86,048

## Abstract

The long term objectives of this project are to define the nature of the
interactions between cartilage aggregating proteoglycans, link protein
and hyaluronic acid and transfer this information to other systems, such
as those of related lymphocyte hyaluronate-receptors.  The complex of
these three components forms the bulk of cartilage by virtue of its
ability to bind large amounts of water.  The complex is constrained
within a network of collagen fibrils and together, the proteoglycan
aggregate and collagen enable cartilage to absorb shock.  The
proteoglycan aggregate probably plays a role in limiting the diffusion
of degradative enzymes, and may play a role in facilitating the diffusion
of slats and low molecular weight molecules.

Link protein is a 40-50 kDa glycoprotein which stabilizes the cartilage
proteoglycan aggregate.  The link protein and the region of proteoglycan
(G1) which binds to hyaluronic acid (HA) are similar in structure.  They
both have a region which is in the immunoglobulin fold family, which has
been shown to be the general site for interaction between link protein
and proteoglycan, and they both have a unique structure which has been
shown to bind to hyaluronate.  This research project aims to analyze the
required amino acids in link protein and G1 in order to define individual
binding sites.  To do this, an evolutionary remote proteoglycan aggregate
(from shark) will be analyzed.  The amino acid sequence of shark link
protein (LP) and shark proteoglycan G1 will be completed and compared to
the same structures in mammalian aggregates with a view to modeling both
the surface topology and the binding sites in these molecules.  Bovine
link protein and aggrecan G1 will be chemically cross-linked and the
cross-linked peptides isolated and identified, defining the relative
orientation of LP and G1 and thus the exact nature of the binding site
between them.  This study will also determine whether LP and G1 are
folded similarly or differently from each other.

Analysis of the structure of the G2 domain in shark aggregating
proteoglycan will also be completed.  This structure is similar to the
region of G1 which binds to HA, but, at least in mammals, does not bind
to HA.  Comparison of G2 structures will enable us to define the
"framework" residues in this domain.  By comparing the G1 domains with
the G2 domains, it will be possible to estimate which residues are
involved in the function of G1 and which are simply required for folding.
This will eventually require site-directed mutagenesis, expression of
individual domains and physical chemistry.  The studies proposed here
will enable meaningful site directed mutagenesis experiments to be
designed.

These analyses will have broader relevance to both closely related
proteoglycans from brain (neurocan), fibroblasts (versican), and also
more remotely related, lymphocyte and fibroblast cell surface,
hyaluronate-binding, proteoglycans (CD44 and TSG-6).  All of these
recently described ...

## Key facts

- **NIH application ID:** 3157151
- **Project number:** 2R01AR035322-07A2
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **SAM.gov UEI:** NKAZLXLL7Z91
- **Principal Investigator:** PETER J. NEAME
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $86,048
- **Award type:** 2
- **Project period:** 1989-04-01 → 1996-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3157151

## Citation

> US National Institutes of Health, RePORTER application 3157151, STRUCTURE AND FUNCTION IN CARTILAGE LINK PROTEIN (2R01AR035322-07A2). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3157151. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*