Docsity
Docsity

Prepare for your exams
Prepare for your exams

Study with the several resources on Docsity


Earn points to download
Earn points to download

Earn points by helping other students or get them with a premium plan


Guidelines and tips
Guidelines and tips

Building Protein Motifs and Models-Proteomics-Lecture Slides, Slides of Proteomics

This lecture was delivered by Dr. Vijay Rao at The Tamil Nadu Dr. M.G.R. Medical University for Proteomics course. It includes: Protein, Motifs, Models, Structure, Threading, Ligands, DNA, Sequence, Transcription, Factors, RNA

Typology: Slides

2011/2012

Uploaded on 07/19/2012

naseem
naseem 🇮🇳

4.5

(22)

82 documents

1 / 87

Toggle sidebar

This page cannot be seen from the preview

Don't miss anything!

bg1
Protein Structure
Computational Goals
Compare all known structures to each other
Compute distances between protein
structures
Classify and organize all structures in a
biologically meaningful way
Discover relationship between structure and
function.
Use known structures and folds to infer
structure from sequence (Protein Threading)
docsity.com
pf3
pf4
pf5
pf8
pf9
pfa
pfd
pfe
pff
pf12
pf13
pf14
pf15
pf16
pf17
pf18
pf19
pf1a
pf1b
pf1c
pf1d
pf1e
pf1f
pf20
pf21
pf22
pf23
pf24
pf25
pf26
pf27
pf28
pf29
pf2a
pf2b
pf2c
pf2d
pf2e
pf2f
pf30
pf31
pf32
pf33
pf34
pf35
pf36
pf37
pf38
pf39
pf3a
pf3b
pf3c
pf3d
pf3e
pf3f
pf40
pf41
pf42
pf43
pf44
pf45
pf46
pf47
pf48
pf49
pf4a
pf4b
pf4c
pf4d
pf4e
pf4f
pf50
pf51
pf52
pf53
pf54
pf55
pf56
pf57

Partial preview of the text

Download Building Protein Motifs and Models-Proteomics-Lecture Slides and more Slides Proteomics in PDF only on Docsity!

Protein Structure

Computational Goals

•^

Compare all known structures to each other

-^

Compute

distances

between

protein

structures

-^

Classify

and

organize

all

structures

in

a

biologically meaningful way

-^

Discover relationship between structure andfunction.

-^

Use

known

structures

and

folds

to

infer

structure from sequence (Protein Threading)

Protein Structure

Computational Goals

•^

Discover conserved substructure domain

-^

Discover conserved substructural motifs

-^

Find

common

folding

patterns

and

structural/functional motifs

-^

Study

interactions

between

proteins

and

other

proteins,

ligands

and

DNA

(Protein

Docking)

-^

Use known structural motifs to infer functionfrom structure

-^

Many more…

What are DNA sequence

motifs?

•^

Sequence motifs are becoming increasinglyimportant in the analysis of gene regulation.

-^

How do we define sequence motifs, and whyshould

we

use

sequence

logos

instead

of

consensus sequences to represent them?

-^

Do

they

have

any

relation

with

binding

affinity?

-^

How do we search for new instances of amotif in this sea of DNA?

Motivation

-^

A central goal in modelling genome regulation isthe

identification

of

transcription

factors

(TFs)

and their target DNA binding sites, expressed asshort nucleotide sequence motif models.

-^

This goal is becoming tractable even for highereukaryotic

genomes

due

to

the

availability

of

annotated

reference

genomes

for

numerous

organisms, large scale protein-DNA interactionand gene expression studies, and advances inregulatory binding site motif inference algorithms.

Goal

AGCCAAGCCAAGCCAAGCCAAGCCA AGCCA

Regulatory

regions

Motif –

Binding site???

Why Bother?

Gene expression

regulation

Co-regulation

UNDERSTAND

From DNA to Protein: In words

DNA = nucleotide sequence•

Alphabet size = 4 (A,C,G,T)

DNA

mRNA (single stranded)

-^

Alphabet size = 4 (A,C,G,U)

mRNA

amino acid sequence

-^

Alphabet size = 20

Amino acid sequence “folds” into 3-dimensional molecule called protein

AATACGAAGTAAAAUACGAAGUAAAsn Thr Lys Stop

Gene expression

  • Process of making a protein from a

gene as template

  • Transcription, then translation• Can be

regulated

GENE

TRANSCRIPTIONACAGTGA

FACTOR

PROTEIN

Transcriptional regulation

GENE

TRANSCRIPTIONACAGTGA

FACTOR

PROTEIN

Transcriptional regulation

17

Anatomy of Transcriptional RegulationWARNING: Terms vary widely in meaning between scientists •^

Core Promoter – Sufficient for initiation oftranscription; orientation dependent

  • TSR – transcription start region
    • Refers to a region rather than specific start site (TSS) -^

TFBS – single transcription factor binding site

-^

Regulatory Regions

  • Proximal/Distal – vague reference to distance from TSR• May be positive (enhancing) or negative (repressing)• Orientation independent (generally)• Modules – Sets of TFBS within a region that function together -^

Transcriptional Unit

-^

DNA sequence transcribed as a single polycistronic mRNA

EXON

TFBS

TATA

TSR

TFBS

TFBS

Core Promoter/Initiation Region (Inr)TFBS

TFBS

Distal Regulatory Region

Proximal Regulatory Region

EXON

TFBS

TFBS Distal R.R.

Module 3

18

Complexity in Transcription

Distal enhancer

Distal enhancer

Proximal enhancer

Core Promoter

Chromatin

20

CpG Islands

-^

DNA methylation occurs in competition with histoneacetylation

-^

Acetylation promotes open chromatin structure that is permissivefor TF binding to DNA

-^

Methylation of DNA inhibits histone acetylation

-^

Certain TFs promote histone acetylation by recruiting acetylases

-^

Methylation occurs on cytosines

-^

Preferentially on cytosine adjacent to guanines (CG dinucleotides,generally referred to as CpG)

-^

Methylated cytosines frequently undergo deamination to formthymidine (CpG -> TpG)

-^

CpG Islands are regions of DNA where CG dinucleotidesoccur at a frequency consistent with C and Gmononucleotide frequencies

-^

Highlight regions in which histones are acetylated – regions ofactive transcription

CpG Islands

•^

Important

to

recognize,

that

promoters

selectively active after early development willnot

be

acetylated

(and

hence

will

be

methylated) in the cell divisions preceding theestablishment of germ cells and therefore willnot have CpG islands.

-^

Lists of genes that have higher or lower CpGfrequencies

than

average

can

misleadingly

appear to have TF binding motifs based onthis compositional characteristic.