Link domain
{{Short description|Protein domain}}
{{Infobox protein family
| Symbol = LINK
| Name = Link domain
| image = PDB 1poz EBI.jpg
| width =
| caption = Structure of the hyaluronan-binding domain of human CD44
| Pfam = PF00193
| Pfam_clan = CL0056
| InterPro = IPR000538
| SMART = SM00445
| PROSITE = PDOC00955
| MEROPS =
| SCOP = 1o7b
| TCDB =
| OPM family =
| OPM protein =
| CAZy =
| CDD = cd01102
}}
A Link domain or Link module, also known as Xlink domain (X for extracellular), is a protein domain that binds to hyaluronic acid.{{cite web|title=Link domain signature and profile|url=http://prosite.expasy.org/cgi-bin/prosite/prosite-search-ac?PDOC00955|website=PROSITE|access-date=30 September 2016|date=December 2004}} It is important in blood cell migration and apoptosis.{{cite journal|vauthors=Yoneda M, Nakamura T, Murai M, Wada H | title=Evidence for the heparin-binding ability of the ascidian Xlink domain and insight into the evolution of the Xlink domain in chordates. | journal=J Mol Evol | year= 2010 | volume= 71 | issue= 1 | pages= 51–9 | pmid=20582409 | doi=10.1007/s00239-010-9363-x | bibcode=2010JMolE..71...51Y | s2cid=10614265 }} The link domain is found in some extracellular proteins in vertebrates such as the hyalectans.{{cite journal|last1=Hynes|first1=RO|last2=Naba|first2=A|title=Overview of the Matrisome--An Inventory of Extracellular Matrix Constituents and Functions|journal=Cold Spring Harbor Perspectives in Biology|date=21 September 2011|volume=4|issue=1|pages=a004903|doi=10.1101/cshperspect.a004903|pmc=3249625|pmid=21937732}} It appears to be involved in extracellular matrix assembly and stability, cell adhesion, and migration.{{cite journal |vauthors=Barta E, Deák F, Kiss I | title = Evolution of the hyaluronan-binding module of link protein | journal = Biochem. J. | volume = 292 | issue = 3| pages = 947–9 |date=June 1993 | pmid = 8318021 | pmc = 1134205 | doi = 10.1042/bj2920947}}
Structure
The structure has been shown to consist of two alpha helices and two antiparallel beta sheets arranged around a large hydrophobic core similar to that of C-type lectin.{{cite journal |vauthors=Kohda D, Morton CJ, Parkar AA, Hatanaka H, Inagaki FM, Campbell ID, Day AJ | title = Solution structure of the link module: a hyaluronan-binding domain involved in extracellular matrix stability and cell migration | journal = Cell | volume = 86 | issue = 5 | pages = 767–75 |date=September 1996 | pmid = 8797823 | doi = 10.1016/S0092-8674(00)80151-8| s2cid = 16347386 | doi-access = free }} This domain contains four conserved cysteines involved in two disulphide bonds. The link domain has also been termed HABM (hyaluronic acid binding module) and PTR (proteoglycan tandem repeat).{{cite journal |vauthors=Brissett NC, Perkins SJ | title = 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 | journal = FEBS Lett. | volume = 388 | issue = 2–3 | pages = 211–6 |date=June 1996 | pmid = 8690089 | doi = 10.1016/0014-5793(96)00576-5| s2cid = 24295651 | doi-access = free }}
Link domain proteins
Proteins which contain the link domain include:
- the hyalectans (a family of proteoglycans): aggrecan, brevican, neurocan and versican, which are expressed in the CNS;
- the cartilage link protein (LP), a proteoglycan that together with HA and aggrecan forms multimolecular aggregates;
- Tumour necrosis factor-inducible protein 6 (TSG-6), which may be involved in cell-cell and cell-matrix interactions during inflammation and tumourigenesis;
- CD44 antigen, the main cell surface receptor for HA.