Laminins [1] 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 [2]. 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:

• Agrin, a basal lamina protein that causes the aggregation of acetylcholine receptors on cultured muscle fibers. It consists of 9 Kazal-like domains, 2 LE domains, and 4 EGF-like domains.
• Perlecan, a multidomain basement membrane heparan sulfate proteoglycan composed of 4 LDLRA domains, 3 LamB domains, 12 LE domains, 14-21 IG- like domains, 3 LamG domains, and 4 EGF-like domains.
• Caenorhabditis elegans basement membrane proteoglycan unc-52, which seems to be involved in myofilament assembly and/or attachment of the myofilament lattice to the cell membrane. The modular architecture is similar to that of perlecan; it consists of 3 LDLRA domains, 2 LamB domains, 7 LE domains and 16 IG-like domains.
• Netrins, proteins that control guidance of CNS commissural axons at the midline and peripheral motor axons. An homolog of netrin is UNC-6 from Caenorhabditis elegans, a component of an extracellular matrix cue that guides dorso-ventral migrations on the epidermis. UNC-6 is required for the guidance of pioneer axons and migrating cells along the body wall. Netrins and UNC-6 are composed of a laminin N-terminal domain (domain VI), 3 LE domains and a complement C3/4/5 C-terminal domain.
• Caenorhabditis elegans hypothetical proteins C54D1.5 and K08C7.3, which both contain a laminin N-terminal domain (domain VI), 10.5 and 21.5 LE domains and a laminin domain IV.
• Caenorhabditis elegans hypothetical protein F33C8.1, that contain two LE domains and 3 EGF-like domains.

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 [5]. 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 [1], 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.