|PROSITE documentation PDOC00961|
Laminins  are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation. They are composed of distinct but related α, β and γ chains. The three chains form a cross-shaped molecule that consist of a long arm and three short globular arms. The long arm consist of a coiled coil structure contributed by all three chains and cross-linked by interchain disulfide bonds.
Beside different types of globular domains each subunit contains, in its first half, consecutive repeats of about 60 amino acids in length that include eight conserved cysteines . The tertiary structure (see <PDB:1KLO>) [3,4] of this domain is remotely similar in its N-terminal to that of the EGF-like module (see <PDOC00021>). It is known as a 'LE' or 'laminin-type EGF-like' domain. The number of copies of the LE domain in the different forms of laminins is highly variable; from 3 up to 22 copies have been found.
A schematic representation of the topology of the four disulfide bonds in the LE domain is shown below.
+-------------------+ +-|-----------+ | +--------+ +-----------------+ | | | | | | | | xxCxCxxxxxxxxxxxCxxxxxxxCxxCxxxxxGxxCxxCxxgaagxxxxxxxxxxxCxx ********************************** sssssssssssssssssssssssssssssssssss
'C': conserved cysteine involved in a disulfide bond 'a': conserved aromatic residue 'G': conserved glycine (lower case = less conserved) 's': region similar to the EGF-like domain '*': position of the pattern
In additions to laminins, the LE domain is also found in:
In mouse laminin γ-1 chain, the seventh LE domain has been shown to be the only one that binds with a high affinity to nidogen . The binding-sites are located on the surface within the loops C1-C3 and C5-C6 [3,4]. Long consecutive arrays of LE domains in laminins form rod-like elements of limited flexibility , which determine the spacing in the formation of laminin networks of basement membranes [6,7].
We derived a signature pattern for the LE domain which covers the C-terminal half of the repeat starting with the fourth conserved cysteine. We also developed a profile that covers the whole LE domain.Note:
Most, but not all LE domains in a given protein are detected by the pattern.Last update:
May 2005 / Text revised; profile added.
PROSITE methods (with tools and information) covered by this documentation:
|1||Authors||Beck K. Hunter I. Engel J.|
|Title||Structure and function of laminin: anatomy of a multidomain glycoprotein.|
|Source||FASEB J. 4:148-160(1990).|
|Title||EGF-like domains in extracellular matrix proteins: localized signals for growth and differentiation?|
|Source||FEBS Lett. 251:1-7(1989).|
|3||Authors||Stetefeld J. Mayer U. Timpl R. Huber R.|
|Title||Crystal structure of three consecutive laminin-type epidermal growth factor-like (LE) modules of laminin gamma1 chain harboring the nidogen binding site.|
|Source||J. Mol. Biol. 257:644-657(1996).|
|4||Authors||Baumgartner R. Czisch M. Mayer U. Poschl E. Huber R. Timpl R. Holak T.A.|
|Title||Structure of the nidogen binding LE module of the laminin gamma1 chain in solution.|
|Source||J. Mol. Biol. 257:658-668(1996).|
|5||Authors||Mayer U. Poeschl E. Gerecke D.R. Wagman D.W. Burgeson R.E. Timpl R.|
|Title||Low nidogen affinity of laminin-5 can be attributed to two serine residues in EGF-like motif gamma 2III4.|
|Source||FEBS Lett. 365:129-132(1995).|
|6||Authors||Yurchenco P.D. Cheng Y.-S.|
|Title||Self-assembly and calcium-binding sites in laminin. A three-arm interaction model.|
|Source||J. Biol. Chem. 268:17286-17299(1993).|
|Source||(In) Extracellular Matrix Assembly and Structure, Yurchenco P.D., Birk D., Mecham R.D., Eds., pp 351-388, Academic Press, San Diego, (1994).|