PROSITE documentation PDOC51841

Lamin-tail (LTD) domain profile

Intermediate filaments (IFs) constitute a major structural element of metazoan cells. They build two distinct systems: one inside the nucleus attached to the inner membrane, and one that is cytoplasmic, which connects intercellular junctional complexes situated at the plasma membrane with the outer nuclear membrane. In both cases, their major function is assumed to be that of a mechanical stress absorber and an integrating device for the entire cytoskeleton. In the nucleus, the IF system is assembled from lamins, which together with an ever increasing number of associated transmembrane and chromatin-binding proteins constitute the nuclear lamina. Despite the large diversity among IF proteins, they all share a similar structural building plan, with a long central α-helical 'rod' domain (see <PDOC00198>) that is flanked by non-α-helical N- and C-terminal end domains called 'head' and 'tail', respectively. Lamins exhibit a highly conserved globular C-terminal lamin-tail domain (LTD) which has the immunoglobulin (Ig) fold (see <PDOC50835>). Invertebrate cytoplasmic IFs share sequence similarity with nuclear lamins and also contain a C-terminal tail domain with homology to the LTD [1,2,3].

Domains homologous to the LTD have been detected in several uncharacterized proteins from phylogenetically diverse bacteria and two archaea, Methanosarcina and Halobacterium. In several bacterial proteins, the LTD cooccurs with membrane-associated hydrolases of the metallo-β-lactamase, synaptojanin, and calcineurin-like phosphoesterase superfamilies. In other secreted or periplasmic bacterial proteins, the LTDs are associated with oligosaccharide-binding domains or are present as multiple tandem repeats in a single protein. These associations suggest a potential role for the prokaryotic LTDs in tethering proteins to the membrane or membrane-associated structures. In contrast to the bacterial homologs, all animal LTDs are closely related and are contained in proteins with a stereotypic architecture. The precursor of the animal LTD might have been acquired via horizontal gene transfer from bacteria relatively late in the evolution of the eukaryotic crown group. Subsequent to this acquisition, a coiled-coil domain, derived from preexisting intermediate filament coil-coils, might have been fused to the N-termini of the LTD [2].

The LTD domain could be involved both in protein and DNA binding [4].

Th LTD domain adopts an Ig-like fold of type s (see <PDB:1IFR>). It consists of a 2-layered sandwich of 9 anti-parallel β-strands arranged in two β-sheets with a Greek key topology. One of the sheets has five β-strands while the other has four. Seven of the 9 strands are present in the classical Ig fold topology [4,5].

Some proteins known to contain a LTD domain are listed below:

• Animal nuclear lamins, together with lamin-associated proteins, maintain nuclear shape and provide a structural support for chromosomes and replicating DNA.
• Chloroflexus aurantiacus Chlo1887.
• Caenorhabditis elegans intermediate filament protein ifc-2 [6].
• Caenorhabditis elegans intermediate filament protein ifd-1.

The profile we developed covers the entire LTD domain.