Worm Breeder's Gazette 11(2): 52
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
As previously reported, the homeodomain of the ceh-14 gene is most similar to the homeodomains of lin-11 and mec-3 (Burglin, T. et al.( 1989), Nature, 341:239; Freyd et al., WBG 10:3). Freyd et al. noticed another region of homology between mec-3 and lin-11 upstream of the homeodomain (WBG 11:1). This region is characterized by a set of absolutely conserved histidine and cysteine residues with a particular spacing. This motif is present twice in mec-3 and lin-11, and has been termed the LIM domain by Freyd and colleagues (personal communication). It has been suggested that this cysteine-rich region is a metal binding domain (Way, WBG 10:3; Freyd et al., WBG 11:1). Sequencing upstream of the ceh-14 homeodomain revealed that this conserved domain is also present in ceh-14 (see figure). However, the spacer region between the homeodomain and the LIM motif is much shorter in ceh-14 than in mec-3. Stars in the figure mark the histidine/cysteine residues, while dashes indicate positions where the same amino acid is found in the first and the second repeat in at least one sequence. Freyd et al. noticed a sequence similarity of the LIM repeat to the rat CRIP gene. Literature searches revealed another gene (ESP1, estradiol-stimulated protein; Nalik, P. et al. (1989), Mol. Cell. Endo., 62:235) that is very homologous to CRIP in the region of the LIM repeat. In contrast to CRIP, ESP1 has a longer amino-terminus, and the sequence conservation in the carboxy-terminal region between CRIP and ESP1 is less pronounced. Underlined amino acids in the CRIP sequence indicate amino acids that are also found in the LIM repeats. The similarity is highest in the CxxC, HxxCxxCxxC region. Downstream of this region, CRIP and ESP1 show a HxxHxxxxxCxxxC motif (indicated by the x above ESP1 ) that might be a different metal binding domain that is not present in the LIM motif. Unfortunately nothing is known about the metal binding capacity of CRIP or ESP1. What metal binds to the LIM repeat? We don't know. However, the closest matching histidine/cysteine pattern to the LIM repeat can be found in the zinc-fingers of the nuclear hormone receptors. In particular, members of the thyroid hormone receptors have the same arrangement of CxxC -loop- HxxCxxCxxC residues, albeit with a shorter loop in the finger (putative zinc-binding cysteine residues shown in bold). However, the cysteine after the absolutely conserved histidine is not conserved in other nuclear hormone receptors (Green, S., et al. (1988) TIG, 4:309). We speculate that the LIM motif could form two zinc fingers that are similar to the first finger of nuclear hormone receptors. [See Figure 1]