Molecular analysis of muskelin identifies a conserved discoidin-like domain that contributes to protein self-association.

Muskelin is an intracellular protein with a C-terminal kelch-repeat domain that was initially characterized as having functional involvement in cell spreading on the extracellular matrix glycoprotein thrombospondin-1. As one approach to understanding the functional properties of muskelin, we have combined bioinformatic and biochemical studies. Through analysis of a new dataset ...
of eight animal muskelins, we showed that the N-terminal region of the polypeptide corresponds to a predicted discoidin-like domain. This domain architecture is conserved in fungal muskelins and reveals a structural parallel between the muskelins and certain extracellular fungal galactose oxidases, although the phylogeny of the two groups appears distinct. In view of the fact that a number of kelch-repeat proteins have been shown to self-associate, co-immunoprecipitation, protein pull-down assays and studies of cellular localization were carried out with wild-type, deletion mutant and point mutant muskelins to investigate the roles of the discoidin-like and kelch-repeat domains. We obtained evidence for cis- and trans-interactions between the two domains. These studies provide evidence that muskelin self-associates through a head-to-tail mechanism involving the discoidin-like domain.
Mesh Terms:
Amino Acid Sequence, Animals, Avian Proteins, Cell Adhesion Molecules, Cell Line, Ciona intestinalis, Conserved Sequence, Dimerization, Drosophila Proteins, Humans, Intracellular Signaling Peptides and Proteins, Kidney, Lectins, Mice, Molecular Sequence Data, Myoblasts, Skeletal, Peptides, Protein Structure, Tertiary, Proteins, Protozoan Proteins, Rats, Repetitive Sequences, Amino Acid, Sequence Alignment, Transfection, Zebrafish, Zebrafish Proteins
Biochem. J.
Date: Jul. 15, 2004
Download Curated Data For This Publication
165742
Switch View:
  • Interactions 1