Use of Microarray analysis in Development Biology - GitHub Pages

Use of Microarray analysis in Development Biology - GitHub Pages

polyQ and other homorepeats Miguel Andrade Faculty of Biology, Johannes Gutenberg University Institute of Molecular Biology Mainz, Germany [email protected] Function of polyQ Martin Schaefer

polyQ in Huntingtin Human Dog Mouse Opossum Chicken Frog Zebrafish Trout Fugu Stickleback Lancelet Capitella Limpet Nematostella

Trichoplax Ciona intestinalis Ciona savignyi D. melanogaster D. mojavensis D. sechellia D. erecta D. yakuba D. grimshawi D. pseudoobscura D. persimilis D. ananassae D. willistoni D. virilis

Schaefer et al (2012) Nucleic Acids Res. Human Dog Mouse Opossum Chicken Frog Zebrafish Trout Fugu Stickleback Lancelet Capitella Limpet

Nematostella Trichoplax Ciona intestinalis Ciona savignyi D. melanogaster D. mojavensis D. sechellia D. erecta D. yakuba D. grimshawi D. pseudoobscura D. persimilis D. ananassae D. willistoni D. virilis

75/4759 4293/4759 354/4759 14 trios P-val < 0.05 1 5 10 50 100 500 1000

partners human polyQ TFs long non polyQ 5 10 1 TFs long non

polyQ polyQ TFs long non polyQ 1 1 2 5 10

50 100 500 1000 5 10 20 50 100 200 500 polyQ partners yeast 50 100 500 1000 50 100 500 1000 5 10 1

partners human polyQ polyQ >14 4-14 no polyQ polyQ SYSTEMS BIOLOGY polyQ >14 4-14

no polyQ 86 human polyQ proteins Nterminal poly Q Cterminal

13 polyQ proteins with near polyP poly Q poly P12 Cterm 109 polyQ regions 54 overlap/near

coiledcoil coil poly ed coil Q 86 human polyQ proteins Nterminal poly Q

Cterminal 13 polyQ proteins with near polyP 40 human polyQ/coile d-coil proteins (no polyP)

coil ed coil poly Q poly P12 Cterm poly Q 36 Nterm 86

human polyQ proteins coil ed coil poly P interacting proteins 49 interactions with

another polyQ protein coil (p-value = ed coil 0.0023) poly P 86 human polyQ proteins

coil ed coil Non-polyQ interacting proteins coil ed coil poly P

Enrichment (p-value < 2.2e-16) polyQ protein unbound Nterminal coil ed coil poly disordere

Q d poly P Cterminal polyQ protein unbound polyQ protein Nterminal

coil ed coil coil ed coil poly disordere Q d poly P

Cterminal protei nX poly Q poly P polyQ protein unbound

polyQ protein bound Nterminal coil ed coil coil ed coil poly disordere

Q d poly P Cterminal protei nX poly Q poly P

ATXN1Q82NT is toxic ATXN1Q82NT aggregates Spyros Petrakis Erich Wanker Petrakis et al. (2012) PLoS Genetics interactors that change ATXN1Q82NT toxicity MED15

PUM1 MED15 GST PUM1 GST Normal polyQ protein CC polyQ disordered

CC partner Normal polyQ protein CC polyQ disordered CC partner Normal polyQ protein CC polyQ disordered

CC partner polyQ alpha-helix Toxic polyQ protein Normal polyQ protein Toxic polyQ protein CC polyQ

disordered CC partner polyQ alpha-helix polyQ beta-aggregates Normal polyQ protein Toxic polyQ protein CC

polyQ disordered polyQ beta-aggregates CC partner polyQ alpha-helix polyQ beta-aggregates

Normal polyQ protein Toxic polyQ protein CC polyQ disordered polyQ beta-aggregates CC partner polyQ

alpha-helix polyQ beta-aggregates Normal polyQ protein Toxic polyQ protein CC polyQ disordered polyQ

beta-aggregates CC partner polyQ alpha-helix non-CC partner polyQ increased beta-aggregates Normal polyQ protein Toxic polyQ protein

CC polyQ disordered polyQ beta-aggregates CC partner polyQ alpha-helix non-CC partner

polyQ increased beta-aggregates Normal polyQ protein Toxic polyQ protein CC polyQ disordered polyQ beta-aggregates

CC partner polyQ alpha-helix non-CC partner polyQ increased beta-aggregates Normal polyQ protein Toxic polyQ protein

CC polyQ disordered polyQ beta-aggregates CC partner polyQ alpha-helix non-CC partner

polyQ increased beta-aggregates Normal polyQ protein Toxic polyQ protein CC polyQ disordered polyQ beta-aggregates

CC partner polyQ alpha-helix non-CC partner polyQ increased beta-aggregates Normal polyQ protein Toxic polyQ protein CC

polyQ disordered polyQ beta-aggregates CC partner polyQ alpha-helix non-CC partner polyQ

increased beta-aggregates HTT network 509 proteins 1319 interactions Erich Wanker Brain network 88 proteins 113 interactions Caudate nucleus network 66 proteins 84 interactions

Matthias Futschik HD dysreg 14 proteins 13 interactions David Fournier Stroedicke et al. (2015) Genome Research CRMP1 MED15

Exercise 1/2. Search for a polyQ insertion in the MR family Open in jalview the alignment of the mineralocorticoid receptor: MR1_fasta.txt Find a polyQ insertion. Do you see any other biased region nearby? Clustering proteins Pablo Mier FastaHerder2 Mier and Andrade-Navarro (2016) J. Comp. Biol.

Clustering proteins Pablo Mier polyQ Escherichia Mier and Andrade-Navarro (2016) J. Comp. Biol. Context of polyX Pablo Mier Mier et al. In revision

Context of polyX Pablo Mier polyQ followed by polyP dependency Mier et al. In revision Context of polyX Pablo Mier Species specific differences Mier et al. In revision Composition of linkers

Daniel Brne Pablo Mier Brne et al. In preparation Composition of linkers Daniel Brne Pablo Mier 38 species: 9 Bacteria 12 Archaea 17 Eukaryota

Brne et al. In preparation Composition of linkers Daniel Brne Pablo Mier DNA binding domain Brne et al. In preparation 3D context of polyQ

polyQ Franziska Totzeck Pablo Mier 3D 3D Totzek et al. Submitted 3D context of polyQ Franziska Totzeck Pablo Mier

Totzek et al. Submitted 3D context of polyQ Franziska Totzeck Pablo Mier Totzek et al. Submitted 3D context of polyQ Franziska Totzeck Pablo Mier

Totzek et al. Submitted 3D context of polyQ Franziska Totzeck Pablo Mier Totzek et al. Submitted polyQ variability Felix Korda (Joachim Burger) Exercise 2/2. Find a 3D of a polyQ ortholog

Go to FASTAHERDER2: http://cbdm-01.zdv.uni-mainz.de/~munoz/fh2/ Find a cluster containing polyQ and a PDB using mode 4 Find the structure surrounding the place of polyQ insertion Any problems? Exercise 2/2. Find a 3D of a polyQ ortholog Go to FASTAHERDER2: http://cbdm-01.zdv.uni-mainz.de/~munoz/fh2/ Find a cluster containing polyQ and a PDB using mode 4 Find the structure surrounding the place of polyQ insertion Any problems? If yes, then use this example: Species: Escherichia coli, PDB yes, and polyQ yes Get the E. coli sequence and the one with polyQ and align

them. Can you see the polyQ insertions? Compare to PDB:4JNF (from DNAK_ECOLI P0A6Y8) Exercise 2/2. Find a 3D of a polyQ ortholog FH2 mode 3 with C4YKT4 / Candida albicans 288 aa with two polyQ Align and compare to P01123 S. cerevisiae 206 alpha-helix and polyQ inserts after. See PDB 2BCG chain Y = YPT1

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