Ácidos nucleicos 14

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Los investigadores utilizan la cristalografía de rayos X para determinar la estructura tridimensional de macromoléculas como los ácidos nucleicos y las proteínas. En esta figura examinaremos el modo en que los investigadores de la Universidad de California, en Riverside, determinaron la estructura de la proteína ribonucleasa, una enzima cuya función implica la unión a una molécula de ácido nucleico. Los investigadores dirigen un haz de rayos X a través de la proteína cristalizada. Los átomos del cristal difractan (desvían) los rayos X en una disposición ordenada. Los rayos X difractados son expuestos a una placa fotográfica y se produce un patrón de puntos conocido como patrón de difracción de rayos X.


Photographic film Diffracted X-rays X-ray source

X-ray beam

Crystal

X-ray diffraction pattern


Utilizando información a partir de los patrones de difracción de rayos X, al igual que la secuencia de aminoácidos determinada por métodos químicos, los científicos construyen un modelo computarizado tridimensional (3D) de la proteína, como este modelo de la proteína ribonucleasa (violeta) unido a una cadena corta de ácido nucleico (verde)


Nucleic acid

X-ray diffraction pattern

3D computer model

Protein







DNA

Synthesis of mRNA in the nucleus mRNA

NUCLEUS CYTOPLASM

mRNA Movement of mRNA into cytoplasm via nuclear pore

Ribosome

Synthesis of protein

Polypeptide

Amino acids


5′ end

Nucleoside Nitrogenous base

Phosphate group Nucleotide 3′ end

Polynucleotide, or nucleic acid

Pentose sugar


Nitrogenous bases Pyrimidines

Cytosine C

Thymine (in DNA) Uracil (in RNA) U T Purines

Adenine A

Guanine G

Pentose sugars

Deoxyribose (in DNA) Nucleoside components

Ribose (in RNA)


5′ end

3′ end Sugar-phosphate backbone Base pair (joined by hydrogen bonding) Old strands Nucleotide about to be added to a new strand

5′ end

New strands

5′ end

3′ end 5′ end

3′ end


Sugar–phosphate backbone

Nitrogenous bases

5′ end

Thymine (T)

Adenine (A)

Cytosine (C)

Phosphate Sugar (deoxyribose) 3′ end

DNA nucleotide

Guanine (G)


Rosalind Franklin

Franklin’s X-ray diffraction photograph of DNA



1 nm 3.4 nm

0.34 nm Key features of DNA structure


5′ end Hydrogen bond

3′ end

3′ end 5′ end Partial chemical structure


Space-filling model


5′ end Hydrogen bond

3′ end

1 nm 3.4 nm

3′ end 0.34 nm Key features of DNA structure

5′ end Partial chemical structure

Space-filling model


Purine + purine: too wide

Pyrimidine + pyrimidine: too narrow

Purine + pyrimidine: width consistent with X-ray data


Sugar

Adenine (A)

Sugar Thymine (T)

Sugar Sugar

Guanine (G)

Cytosine (C)


Sugar

Sugar Adenine (A)

Thymine (T)


Sugar

Sugar

Guanine (G)

Cytosine (C)



2 nm DNA double helix Histones

Histone tails Histone H1

Linker DNA (“string”)

Nucleosome (“bead”)

Nucleosomes (10-nm fiber)

10 nm


30 nm

Nucleosome 30-nm fiber


Protein scaffold Loops 300 nm Looped domains (300-nm fiber)

Scaffold


700 nm

1,400 nm

Metaphase chromosome


Signal

NUCLEUS Chromatin

DNA

Gene available for transcription Gene Transcription

RNA

Exon Primary transcript Intro RNA processing Tail

Cap

mRNA in nucleus Transport to cytoplasm

CYTOPLASM mRNA in cytoplasm Degradation of mRNA

Translation

Polypeptide Cleavage Chemical modification Transport to cellular destination Active protein Degradation of protein Degraded protein






Histone tails

DNA double helix

Amino acids available for chemical modification

Histone tails protrude outward from a nucleosome

Unacetylated histones

Acetylated histones

Acetylation of histone tails promotes loose chromatin structure that permits transcription


Enhancer (distal control elements)

Proximal control elements Exon

Intron

Exon

Poly-A signal Termination sequence region Intron Exon

DNA Upstream

Promoter Primary RNA transcript 5′ (pre-mRNA)

Transcription

Exon

Intron

Intron RNA

Downstream

Poly-A signal Exon Intron Exon Cleaved 3′ end of primary transcript RNA processing: Cap and tail added; introns excised and exons spliced together

Coding segment mRNA

3′ 5′ Cap

5′ UTR (untranslated region)

Start codon

Stop codon

Poly-A 3′ UTR (untranslated tail region)


Distal control element

Activators

Promoter Gene

DNA TATA box

Enhancer

General transcription factors DNA-bending protein Group of mediator proteins

RNA polymerase II

RNA polymerase II

Transcription Initiation complex

RNA synthesis


Liver cell nucleus

Available activators Enhancer

Control elements

Lens cell nucleus

Available activators

Promoter

Albumin gene

Crystallin gene

Albumin gene not expressed

Albumin gene expressed

Crystallin gene not expressed Liver cell

Crystallin gene expressed Lens cell


Exons

DNA

Primary RNA transcript RNA splicing mRNA

or


Protein complex

Degradation of mRNA

Dicer OR miRNA Target mRNA

Hydrogen bond

Blockage of translation


Proteasome and ubiquitin to be recycled

Ubiquitin Proteasome

Protein to be degraded

Ubiquitinated protein Protein entering a proteasome

Protein fragments (peptides)


Proto-oncogene DNA

Translocation or transposition: gene moved to new locus, under new controls

Gene amplification: multiple copies of the gene

New promoter

Normal growth-stimulating protein in excess

Point mutation within a control element

Oncogene

Normal growth-stimulating protein in excess

Normal growth-stimulating protein in excess

Point mutation within the gene

Oncogene

Hyperactive or degradationresistant protein


MUTATION

Growth factor

Hyperactive Ras protein (product of oncogene issues signals on its own.

G protein Cell cycle-stimulating pathway

Receptor

Protein kinases (phosphorylation cascade)

NUCLEUS Transcription factor (activator)

DNA Gene expression

Protein that stimulates the cell cycle


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