Presentation is loading. Please wait.

Presentation is loading. Please wait.

polyQ and other homorepeats

Published byDinah Gray Modified over 6 years ago

Similar presentations

Presentation on theme: "polyQ and other homorepeats"— Presentation transcript:

1 polyQ and other homorepeats
Miguel Andrade Faculty of Biology, Johannes Gutenberg University Institute of Molecular Biology Mainz, Germany

2 Schaefer et al (2012) Nucleic Acids Res.
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.

3 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 14 families: Human polyQ, fly polyQ, fish no polyQ. P-value < 0.05 75/4759 4293/4759 354/4759 14 trios P-val < 0.05

4 human partners polyQ TFs long non polyQ
partners polyQ TFs long non polyQ

5 polyQ non polyQ TFs long yeast human partners polyQ TFs long non polyQ
human partners polyQ TFs long non polyQ Systems Biology no polyQ polyQ >14 polyQ 4-14 partners

6 proteins with near polyP
86 human polyQ proteins polyP polyQ 13 polyQ proteins with near polyP 12 C-term polyQ coiled coil 109 polyQ regions 54 overlap/near N-terminal polyQ Run of P>=3 max dist 3. C-terminal

7 40 human polyQ/coiled-coil proteins
(no polyP) 86 human polyQ proteins polyP polyQ 13 polyQ proteins with near polyP 12 C-term polyQ coiled coil N-terminal 36 N-term polyQ Run of P>=3 max dist 3. C-terminal

8 86 human polyQ proteins interacting proteins polyP coiled coil polyP coiled coil 49 interactions with another polyQ protein (p-value = )

9 Non-polyQ interacting proteins
86 human polyQ proteins Non-polyQ interacting proteins polyP coiled coil coiled coil Enrichment (p-value < 2.2e-16)

10 polyQ protein N-terminal C-terminal polyP polyQ coiled coil
unbound polyP polyQ disordered coiled coil

11 polyQ protein polyQ protein protein X N-terminal coiled coil
C-terminal unbound polyP polyQ disordered coiled coil polyQ protein protein X polyP coiled coil polyQ

12 polyQ protein polyQ protein protein X N-terminal coiled coil
C-terminal unbound polyP polyQ disordered coiled coil polyQ protein bound protein X coiled coil polyQ polyP

13 ATXN1Q82NT is toxic ATXN1Q82NT aggregates Spyros Petrakis Erich Wanker
Toxicity: transfection into COS-1 cells (monkey fibroblasts), caspase activity assay Production of aggregates: filter retardation assay Erich Wanker Petrakis et al. (2012) PLoS Genetics

14 interactors that change ATXN1Q82NT toxicity

15 MED15 PUM1

16 MED15 GST PUM1

17 GST

18

19

20 Normal polyQ protein CC polyQ disordered CC partner

21 Normal polyQ protein CC polyQ disordered CC partner

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

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

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

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

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

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

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

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

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

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

32 Caudate nucleus network 66 proteins 84 interactions
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

33

34 CRMP1 MED15 CRMP is the drosophila protein

35 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?

36 Clustering proteins FastaHerder2 Pablo Mier
Mier and Andrade-Navarro (2016) J. Comp. Biol.

37 Clustering proteins polyQ Escherichia Pablo Mier
Mier and Andrade-Navarro (2016) J. Comp. Biol.

38 Context of polyX Pablo Mier Mier et al. In revision

39 polyQ followed by polyP dependency
Context of polyX Pablo Mier polyQ followed by polyP dependency Mier et al. In revision

40 Species specific differences
Context of polyX Pablo Mier Species specific differences Mier et al. In revision

41 Composition of linkers
Daniel Brüne Pablo Mier Brüne et al. In preparation

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

43 Composition of linkers
Daniel Brüne Pablo Mier DNA binding domain Brüne et al. In preparation

44 3D context of polyQ 3D 3D Franziska Totzeck Pablo Mier polyQ
Totzek et al. Submitted

45 3D context of polyQ Franziska Totzeck Pablo Mier
Totzek et al. Submitted

46 3D context of polyQ Franziska Totzeck Pablo Mier
Totzek et al. Submitted

47 3D context of polyQ Franziska Totzeck Pablo Mier
Totzek et al. Submitted

48 3D context of polyQ Franziska Totzeck Pablo Mier
Totzek et al. Submitted

49 polyQ variability Felix Korda (Joachim Burger)

50

51 Exercise 2/2. Find a 3D of a polyQ ortholog
Go to FASTAHERDER2: Find a cluster containing polyQ and a PDB using mode 4 Find the structure surrounding the place of polyQ insertion Any problems?

52 Exercise 2/2. Find a 3D of a polyQ ortholog
Go to FASTAHERDER2: 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)

53 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

Download ppt "polyQ and other homorepeats"

Similar presentations

GBrowse at TAIR Philippe Lamesch TAIR curator. Seqviewer.

GBrowse at TAIR Philippe Lamesch TAIR curator. Seqviewer.
Part I: Tips and Techniques from curators GBrowse at TAIR David Swarbreck.

Part I: Tips and Techniques from curators GBrowse at TAIR David Swarbreck.
NUCLEIC ACIDS {DNA;RNA} w 1. What are they? w 2. Where are they found? w 3. What are their functions? w 4. What is a nucleotide? Draw one. w (pages 219.

NUCLEIC ACIDS {DNA;RNA} w 1. What are they? w 2. Where are they found? w 3. What are their functions? w 4. What is a nucleotide? Draw one. w (pages 219.
Secondary structure prediction. Amino acid sequence -> Secondary structure Alpha helix Beta strand Disordered/coil 70% accuracy 1991, 81% accuracy in.

Secondary structure prediction. Amino acid sequence -> Secondary structure Alpha helix Beta strand Disordered/coil 70% accuracy 1991, 81% accuracy in.
Protein Interactions and Disease Audry Kang 7/15/2013.

Protein Interactions and Disease Audry Kang 7/15/2013.
Comparative Genomics of the Eukaryotes

Comparative Genomics of the Eukaryotes
Practical session 2b Introduction to 3D Modelling and threading 9:30am-10:00am 3D modeling and threading 10:00am-10:30am Analysis of mutations in MYH6.

Practical session 2b Introduction to 3D Modelling and threading 9:30am-10:00am 3D modeling and threading 10:00am-10:30am Analysis of mutations in MYH6.
Structural Bioinformatics R. Sowdhamini National Centre for Biological Sciences Tata Institute of Fundamental Research Bangalore, INDIA.

Structural Bioinformatics R. Sowdhamini National Centre for Biological Sciences Tata Institute of Fundamental Research Bangalore, INDIA.
Genomes School B&I TCD Bioinformatics May 2010. Genome sizes Completed eukaryotic nuclear genomes Type of organismSpeciesGenome size (10 6 base pairs)

Genomes School B&I TCD Bioinformatics May Genome sizes Completed eukaryotic nuclear genomes Type of organismSpeciesGenome size (10 6 base pairs)
The FREAKS Session 3.1: Repeats Session 3.2: Biased regions Miguel Andrade Johannes-Gutenberg University of Mainz of PROTEIN SEQUENCE.

The FREAKS Session 3.1: Repeats Session 3.2: Biased regions Miguel Andrade Johannes-Gutenberg University of Mainz of PROTEIN SEQUENCE.
Repeats and composition bias. Repeats Frequency 14% proteins contains repeats (Marcotte et al, 1999) 1: Single amino acid repeats. 2: Longer imperfect.

Repeats and composition bias. Repeats Frequency 14% proteins contains repeats (Marcotte et al, 1999) 1: Single amino acid repeats. 2: Longer imperfect.
Conserve Fibroblast growth factor 8 (fgf 8) domains Ana Tomas Judith Paridaen Susana Domingues.

Conserve Fibroblast growth factor 8 (fgf 8) domains Ana Tomas Judith Paridaen Susana Domingues.
Web Databases for Drosophila Introduction to FlyBase and Ensembl Database Wilson Leung6/06.

Web Databases for Drosophila Introduction to FlyBase and Ensembl Database Wilson Leung6/06.
Conservation and Evolution of Cis-Regulatory Systems Tal El-Hay Computational Biology Seminar חנוכה תשסו December 2005.

Conservation and Evolution of Cis-Regulatory Systems Tal El-Hay Computational Biology Seminar חנוכה תשס"ו December 2005.
Searching for Transcription Start Sites in Drosophila

Searching for Transcription Start Sites in Drosophila
Overview of the Drosophila modENCODE hybrid assemblies Wilson Leung01/2014.

Overview of the Drosophila modENCODE hybrid assemblies Wilson Leung01/2014.
Brief Overview of Macromolecules DNA, RNA, and Proteins.

Brief Overview of Macromolecules DNA, RNA, and Proteins.
Repeats and composition bias. Repeats Frequency 14% proteins contains repeats (Marcotte et al, 1999) 1: Single amino acid repeats. 2: Longer imperfect.

Repeats and composition bias. Repeats Frequency 14% proteins contains repeats (Marcotte et al, 1999) 1: Single amino acid repeats. 2: Longer imperfect.
You have worked for 2 years to isolate a gene involved in axon guidance. You sequence the cDNA clone that contains axon guidance activity. The sequence.

You have worked for 2 years to isolate a gene involved in axon guidance. You sequence the cDNA clone that contains axon guidance activity. The sequence.
1 How do regulatory networks evolve? Module = group of genes co-regulated by the same regulatory system * Evolution of individual gene targets Gain or.

1 How do regulatory networks evolve? Module = group of genes co-regulated by the same regulatory system * Evolution of individual gene targets Gain or.

Similar presentations

Ads by Google