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The Tektin Family of Microtubule-Stabilizing Proteins Linda a Amos

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The Tektin Family of Microtubule-Stabilizing Proteins Linda a Amos View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by PubMed Central Protein family review The tektin family of microtubule-stabilizing proteins Linda A Amos Address: MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK. Email: [email protected] Published: 29 July 2008 Genome Biology 2008, 9:229 (doi:10.1186/gb-2008-9-7-229) The electronic version of this article is the complete one and can be found online at http://genomebiology.com/2008/9/7/229 © 2008 BioMed Central Ltd Summary Tektins are insoluble α-helical proteins essential for the construction of cilia and flagella and are found throughout the eukaryotes apart from higher plants. Being almost universal but still fairly free to mutate, their coding sequences have proved useful for estimating the evolutionary relationships between closely related species. Their protein molecular structure, typically consisting of four coiled-coil rod segments connected by linkers, resembles that of intermediate filament (IF) proteins and lamins. Tektins assemble into continuous rods 2 nm in diameter that are probably equivalent to subfilaments of the 10 nm diameter IFs. Tektin and IF rod sequences both have a repeating pattern of charged amino acids superimposed on the seven-amino-acid hydrophobic pattern of coiled-coil proteins. The length of the repeat segment matches that of tubulin subunits, suggesting that tektins and tubulins may have coevolved, and that lamins and IFs may have emerged later as modified forms of tektin. Unlike IFs, tektin sequences include one copy of a conserved peptide of nine amino acids that may bind tubulin. The 2 nm filaments associate closely with tubulin in doublet and triplet microtubules of axonemes and centrioles, respectively, and help to stabilize these structures. Their supply restricts the assembled lengths of cilia and flagella. In doublet microtubules, the 2 nm filaments may also help to organize the longitudinal spacing of accessory structures, such as groups of inner dynein arms and radial spokes. Gene organization and evolutionary history roles [11,12,14-20]. A limited number of interacting protein Genes for tektins are found throughout the animal kingdom partners leaves tektin sequences relatively free to mutate. (for example, they have been sequenced in mammals, fish, Thus, an essential testis-specific isoform has been included sea urchins, insects, and nematodes) and also in algal as one of the nuclear genes used to estimate the evolutionary species (for example, the unicellular Chlamydomonas) but distances between closely related species [21,30]. not in flowering plants; that is, they occur in any eukaryotic organism that develops cilia or flagella [1-30]. Their relation- Tektins are related to intermediate filament (IF) proteins ships (Figure 1) suggest a complex evolutionary history [1,5,31,32] and nuclear lamins [33-35], whose sequences involving gene duplications and subsequent losses of un- also show evidence of gene duplication. Within the rod necessary genes. Some organisms have a single tektin; for domains of both tektins and IFs, the longitudinal repeating example, zebrafish have only tektin 2, a testis protein. pattern of hydrophobic and charged amino acids suggests Others have several: for example, sea urchins use three in that their ancestral protein may have evolved in tandem with their sperm tails; humans have at least six, some of which tubulin, whose globular monomers polymerize into proto- are specific to testis whereas others occur also in cilia and filaments with a 4 nm repeat. This spacing, corresponding to centrioles in cells in other tissues. The human tektin genes 28 residues along a coiled-coil, would have arisen quite are all found on different chromosomes. Different tektins simply in an ancestral tektin as groups of four heptads. from one species vary more than equivalent sequences from However, other coiled-coil proteins do have different patterns different species, suggesting that each type may have specific of charge, and different superhelix repeats; indeed, the Genome Biology 2008, 9:229 http://genomebiology.com/2008/9/7/229 Genome Biology 2008, Volume 9, Issue 7, Article 229 Amos 229.2 TEKT3_HUMAN/99-482 Q53EV5_HUMAN/99-482 Q4R620_MACFA/99-220 Tektin 3 Q5SXS5_MOUSE/99-482 TEKT3_MOUSE/99-482 Q4V8G8_RAT/99-482 Q7T0V0_XENLA/99-482 Q5M7C9_XENLA/99-478 Xenopus tektins Q28HF9_XENTR/99-482 Q4RYE7_TETNG/96-479 Q6AYH7_RAT/95-478 Q14BE9_MOUSE/95-415 TEKT5_MACFA/94-477 A1L3Z3_HUMAN/94-477 Tektin 5 TEKT5_HUMAN/94-477 TEKT5_BOVIN/98-481 Q8I044_DROME/131-514 Q8I0K9_DROME/212-595 Drosophila tektins Q8IRZ1_DROME/212-595 Q7PRZ5_ANOGA/103-486 Q8NAE5_HUMAN/32-148 Q5BTG0_SCHJA/5-68 Q5DEG3_SCHJA/7-95 Q3SWV3_HUMAN/32-146 More human tektins Q5I6S4_9NEOP/40-242 in these groups Q6GMR3_HUMAN/32-129 Q8TEH8-HUMAN/50-115 TEKTA_MOUSE/56-439 TEKT4_RAT/56-439 TEKT4_BOVIN/56-439 Q4R8L6_MACFA/56-381 TEKT4_HUMAN/44-427 Tektin 4 Q4RZW8_TETNG/51-434 Q1ED25_BRARE/72-455 Q4V9M4_BRARE/67-450 Q8WZ33_HUMAN/54-116 TETK4-XENLA/55-438 Q8T884_CIOIN/56-439 Q9UOE3_STRPU/71-454 Tektin A1 Q9Z285_MOUSE/16-399 Q5NBU4_MOUSE/16-399 TEKT1_MOUSE/16-399 TEKT1_RAT/16-399 Tektin 1 TEKT1_CANFA/16-399 TETK1_HUMAN/16-399 TEKT1_BOVIN/16-399 Q6IP53_XENLA/16-399 Q28IK6_XENTR/16-399 Xenopus tektins Q0VFM7_XENTR/16-399 Q26623_STRPU/16-399 Tektin C1 Q50306_BRARE/12-395 Q5C3R1_SCHJA_16-192 Q5OEG3_SCHJA/7-95 TETK2_HUMAN/17-399 TETK2_MACFA/17-399 TEKT2_BOVIN/17-399 Tektin 2 TEKT2_MOUSE/17-399 TEKT2_RAT/17-399 Q1W6C3_MESAU/1-86 Q7ZTQ3_XENLA/17-399 Q68EP8_XENTR/17-399 Xenopus tektins Q3B8JA_XENLA/17-399 Q8T883_CIOIN/17-399 TKB1_STRPU/1-372 Tektin B1 Q6TEQ4_BRARE/17-402 Q567M1_BRARE/17-399 Q1L952_BRARE/17-399 Q1L953_BRARE/1-258 Q4RCS5_TETNG/1-67 Q8I1F3_DROER/21-403 A0AMS9_DROME/21-403 Drosophila tektins Q9W1V2_DROME/21-403 A0AMS9_DROSI/21-403 Q291Y4_DROPS/21-403 Q7Q482_ANOGA/21-403 Q0IFA2_AEDAE/21-403 Q5C2Q8_SCHJA/16_202 Q8T3Z0_DROME/35-418 Q29E50_DROPS/35-418 Q7QJ75_ANOGA/34-318 Q17ND5_AEDAE/163-505 Q619E4_CAEBR/230-617 Q21641_CAEEL/231-623 Nematode tektins Q7Y084_CHLRE/36-421 Neoptera tektins Figure 1 Distribution of tektin sequences. Phylogenetic tree showing the relationships between known tektin sequences. The three original sequences obtained from the sea urchin Strongylocentrotus purpuratus are labeled in pink, mammalian tektins 1-3, and 5 in green, and mammalian tektin 4 (found in dense fibers [45]) in blue. Neoptera is a taxonomic group that includes most of the winged insects. Modified output from pfam: family: tektin (pf03148) [66,67]. Species abbreviations [66]: AEDAE, Aedes aegypti; ANOGA, Anopheles gambiae; BOVIN, Bos taurus; BRARE, Danio rerio; CAEBR, Caenorhabditis briggsae; CAEEL, Caenorhabditis elegans; CANFA, Canis familiaris; CHLRE, Chlamydomonas reinhardtii; CIOIN, Ciona intestinalis; DROER, Drosophila erecta; DROME, Drosophila melanogaster; DROPS, Drosophila pseudoobscura; DROSI, Drosophila simulans; MACFA, Macaca fascicularis; MESAU, Mesocricetus auratus (golden hamster); MOUSE, Mus musculus; NEOP, Neoptera sp.; RAT, Rattus norvegicus; SCHJA, Schistosoma japonicum; STRPU, Strongylocentrotus purpuratus; TETNG, Tetraodon nigroviridis; XENLA, Xenopus laevis; XENTR, Xenopus tropicalis. Genome Biology 2008, 9:229 http://genomebiology.com/2008/9/7/229 Genome Biology 2008, Volume 9, Issue 7, Article 229 Amos 229.3 charge pattern of tropomyosin matches the 5.5 nm periodicity half is further divided into two, so the original protein was of subunits in actin filaments [36]. Thus, it is not clear perhaps equivalent to a quarter of a tektin. The four α-helical whether a tubulin-like or a tektin-like protein might have rod-domain segments, 1A, 1B, 2A, and 2B, are connected by existed first. linkers [5-7]. Because of divergence between the half- domains, the tektin signature nonapeptide sequence (usually Bacteria have a homolog of tubulin, FtsZ (a protein involved RPNVELCRD, variations are shown in Figure 2) occurs only in septum formation during cell division), that also forms in the middle of the second half (only in the linker between linear protofilaments with a similar longitudinal spacing, the 2A and 2B helices, although there are other conserved although the spacing is a little longer, approximately 4.3 nm, cysteines in the loops at either end of 1B and 2B [9], see and the protofilaments do not associate to form micro- Figure 2a). The high degree of conservation of the nona- tubules [37,38]. Is one of FtsZ’s protein partners tektin-like? peptide suggests a functionally important tektin-specific Several of the proteins known to interact with FtsZ [39,40] domain, most likely for binding to tubulin, but this has not appear to form coiled-coil dimers (for example, EzrA, SlmA, been shown experimentally. At a similar point, IF and and ZapA) but it is difficult to draw parallels with the eukary- lamins have just a stutter in the heptad pattern of hydro- otic tubulin-tektin association as FtsZ does not assemble phobic amino acids, to show where a connecting link into any long-term stable structure. A coiled-coil protein between two stretches of coiled-coil once existed (see the that forms stable filaments in Caulobacter crescentus has lamin plot in Figure 2b). Superimposed on the hydrophobic been investigated and shows a basic similarity to IF proteins heptad repeats, there are longer repeating patterns of [41,42] but this might be coincidental; for example, muscle charged amino acids. Three charge repeats, of approximately myosins bundle into filaments but are not considered to be nine residues each, define lengths of IF rod of approximately IF-like. The spirochete coiled-coil protein Scc [43] also 4 nm [33]. The charge pattern is actually less clear in tektins forms stable filaments, but the molecules seem to be [5], but each quarter-rod segment still matches an 8 nm continuous coiled-coils without any of the breaks or ‘stutters’ tubulin heterodimer. (short interruptions in the repeating pattern of residues) characteristic of IFs. Something in Spirochaeta halophila Tektins were first isolated from sea urchin sperm tails. Long was found to react with anti-tektin antibodies [44] but no continuous filaments run along the doublet microtubules of candidate sequence has been identified in the genome.
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