Structural bioinformatics predicts that the Retinitis Pigmentosa-28 protein of unknown function FAM161A is a homologue of the microtubule nucleation factor Tpx2 [version 1; peer review: 2 approved]
Background: FAM161A is a microtubule-associated protein conserved widely across eukaryotes, which is mutated in the inherited blinding disease Retinitis Pigmentosa-28. FAM161A is also a centrosomal protein, being a core component of a complex that forms an internal skeleton of centrioles. Despite th...
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2020-08-01
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| Series: | F1000Research |
| Online Access: | https://f1000research.com/articles/9-1052/v1 |
| _version_ | 1818562363306016768 |
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| author | Timothy P. Levine |
| author_facet | Timothy P. Levine |
| author_sort | Timothy P. Levine |
| collection | DOAJ |
| description | Background: FAM161A is a microtubule-associated protein conserved widely across eukaryotes, which is mutated in the inherited blinding disease Retinitis Pigmentosa-28. FAM161A is also a centrosomal protein, being a core component of a complex that forms an internal skeleton of centrioles. Despite these observations about the importance of FAM161A, current techniques used to examine its sequence reveal no homologies to other proteins. Methods: Sequence profiles derived from multiple sequence alignments of FAM161A homologues were constructed by PSI-BLAST and HHblits, and then used by the profile-profile search tool HHsearch, implemented online as HHpred, to identify homologues. These in turn were used to create profiles for reverse searches and pair-wise searches. Multiple sequence alignments were also used to identify amino acid usage in functional elements. Results: FAM161A has a single homologue: the targeting protein for Xenopus kinesin-like protein-2 (Tpx2), which is a strong hit across more than 200 residues. Tpx2 is also a microtubule-associated protein, and it has been shown previously by a cryo-EM molecular structure to nucleate microtubules through two small elements: an extended loop and a short helix. The homology between FAM161A and Tpx2 includes these elements, as FAM161A has three copies of the loop, and one helix that has many, but not all, properties of the one in Tpx2. Conclusions: FAM161A and its homologues are predicted to be a previously unknown variant of Tpx2, and hence bind microtubules in the same way. This prediction allows precise, testable molecular models to be made of FAM161A-microtubule complexes. |
| first_indexed | 2024-12-14T01:02:46Z |
| format | Article |
| id | doaj.art-83ac4c9a305545bf981b9d090e01f18d |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-12-14T01:02:46Z |
| publishDate | 2020-08-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | F1000Research |
| spelling | doaj.art-83ac4c9a305545bf981b9d090e01f18d2022-12-21T23:23:09ZengF1000 Research LtdF1000Research2046-14022020-08-01910.12688/f1000research.25870.128550Structural bioinformatics predicts that the Retinitis Pigmentosa-28 protein of unknown function FAM161A is a homologue of the microtubule nucleation factor Tpx2 [version 1; peer review: 2 approved]Timothy P. Levine0UCL Institute of Ophthalmology, University College London, London, EC1V 9EL, UKBackground: FAM161A is a microtubule-associated protein conserved widely across eukaryotes, which is mutated in the inherited blinding disease Retinitis Pigmentosa-28. FAM161A is also a centrosomal protein, being a core component of a complex that forms an internal skeleton of centrioles. Despite these observations about the importance of FAM161A, current techniques used to examine its sequence reveal no homologies to other proteins. Methods: Sequence profiles derived from multiple sequence alignments of FAM161A homologues were constructed by PSI-BLAST and HHblits, and then used by the profile-profile search tool HHsearch, implemented online as HHpred, to identify homologues. These in turn were used to create profiles for reverse searches and pair-wise searches. Multiple sequence alignments were also used to identify amino acid usage in functional elements. Results: FAM161A has a single homologue: the targeting protein for Xenopus kinesin-like protein-2 (Tpx2), which is a strong hit across more than 200 residues. Tpx2 is also a microtubule-associated protein, and it has been shown previously by a cryo-EM molecular structure to nucleate microtubules through two small elements: an extended loop and a short helix. The homology between FAM161A and Tpx2 includes these elements, as FAM161A has three copies of the loop, and one helix that has many, but not all, properties of the one in Tpx2. Conclusions: FAM161A and its homologues are predicted to be a previously unknown variant of Tpx2, and hence bind microtubules in the same way. This prediction allows precise, testable molecular models to be made of FAM161A-microtubule complexes.https://f1000research.com/articles/9-1052/v1 |
| spellingShingle | Timothy P. Levine Structural bioinformatics predicts that the Retinitis Pigmentosa-28 protein of unknown function FAM161A is a homologue of the microtubule nucleation factor Tpx2 [version 1; peer review: 2 approved] F1000Research |
| title | Structural bioinformatics predicts that the Retinitis Pigmentosa-28 protein of unknown function FAM161A is a homologue of the microtubule nucleation factor Tpx2 [version 1; peer review: 2 approved] |
| title_full | Structural bioinformatics predicts that the Retinitis Pigmentosa-28 protein of unknown function FAM161A is a homologue of the microtubule nucleation factor Tpx2 [version 1; peer review: 2 approved] |
| title_fullStr | Structural bioinformatics predicts that the Retinitis Pigmentosa-28 protein of unknown function FAM161A is a homologue of the microtubule nucleation factor Tpx2 [version 1; peer review: 2 approved] |
| title_full_unstemmed | Structural bioinformatics predicts that the Retinitis Pigmentosa-28 protein of unknown function FAM161A is a homologue of the microtubule nucleation factor Tpx2 [version 1; peer review: 2 approved] |
| title_short | Structural bioinformatics predicts that the Retinitis Pigmentosa-28 protein of unknown function FAM161A is a homologue of the microtubule nucleation factor Tpx2 [version 1; peer review: 2 approved] |
| title_sort | structural bioinformatics predicts that the retinitis pigmentosa 28 protein of unknown function fam161a is a homologue of the microtubule nucleation factor tpx2 version 1 peer review 2 approved |
| url | https://f1000research.com/articles/9-1052/v1 |
| work_keys_str_mv | AT timothyplevine structuralbioinformaticspredictsthattheretinitispigmentosa28proteinofunknownfunctionfam161aisahomologueofthemicrotubulenucleationfactortpx2version1peerreview2approved |