Levine, TP;
(2020)
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
, 9
, Article 1052. 10.12688/f1000research.25870.1.
Preview |
Text
7ff95c08-f129-4cda-8e6b-a6ccbc3603d3_25870_-_tim_levine.pdf - Published Version Download (2MB) | Preview |
Abstract
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.
| Type: | Article |
|---|---|
| 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] |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.12688/f1000research.25870.1 |
| Publisher version: | https://doi.org/10.12688/f1000research.25870.1 |
| Language: | English |
| Additional information: | © 2020 Levine TP. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Structural Bioinformatics, Microtubule Associated Protein, Centrosome, Primary Cilium, Retinitis Pigmentosa, Nucleation Factor, Tpx2, FAM161A |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10109149 |
Archive Staff Only
 |
View Item |
