title: The evolution of filamin-a protein domain repeat perspective.
abstract: Particularly in higher eukaryotes, some protein domains are found in tandem repeats, performing broad functions often related to cellular organization. For instance, the eukaryotic protein filamin interacts with many proteins and is crucial for the cytoskeleton. The functional properties of long repeat domains are governed by the specific properties of each individual domain as well as by the repeat copy number. To provide better understanding of the evolutionary and functional history of repeating domains, we investigated the mode of evolution of the filamin domain in some detail. Among the domains that are common in long repeat proteins, sushi and spectrin domains evolve primarily through cassette tandem duplications while scavenger and immunoglobulin repeats appear to evolve through clustered tandem duplications. Additionally, immunoglobulin and filamin repeats exhibit a unique pattern where every other domain shows high sequence similarity. This pattern may be the result of tandem duplications, serve to avert aggregation between adjacent domains or it is the result of functional constraints. In filamin, our studies confirm the presence of interspersed integrin binding domains in vertebrates, while invertebrates exhibit more varied patterns, including more clustered integrin binding domains. The most notable case is leech filamin, which contains a 20 repeat expansion and exhibits unique dimerization topology. Clearly, invertebrate filamins are varied and contain examples of similar adjacent integrin-binding domains. Given that invertebrate integrin shows more similarity to the weaker filamin binder, integrin β3, it is possible that the distance between integrin-binding domains is not as crucial for invertebrate filamins as for vertebrates.
authors.affiliation: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Science for Life Laboratory, Bioinformatics Infrastructure for Life Sciences, Stockholm University, SE-17121 Solna, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Light
authors.forename: Rauan
authors.initials: R
authors.lastname: Sagit
authors.forename: Sujay S
authors.initials: SS
authors.lastname: Ithychanda
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
authors.forename: Arne
authors.initials: A
authors.lastname: Elofsson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016000:Cluster Analysis; D016384:Consensus Sequence; D003285:Contractile Proteins / Q000737:chemistry* / Q000235:genetics*; D019143:Evolution, Molecular; D064448:Filamins; D006801:Humans; D008390:Markov Chains; D008840:Microfilament Proteins / Q000737:chemistry* / Q000235:genetics*; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D020449:Repetitive Sequences, Amino Acid; D020539:Sequence Analysis, Protein
chemical_list: D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins