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Biology Lectures – winter term 2008 1 st year of Pharmacy study

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Page 1: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

BiologyLectures – winter term 2008

1st year of Pharmacy study

Page 2: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Chemical composition of living matter – chemical basis of life. Atoms, molecules, organic compounds – carbohydrates, lipids, proteins, nucleic acids

3rd Lecture

Page 3: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace
Page 4: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Atoms-protons,neutrons,electrons

electrons electrons

Page 5: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Macroelements

H,O,C,N,P,S,Na,K,Cl,Fe,Mg

Microelements

I,Mn,F,Zn,Cu,Co,Se,.......

Page 6: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Bonds of atoms

Page 7: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

MoleculesBond – ionic, covalent, polar and non-polar

metán

Sodík Chlór NaCl

Page 8: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

H2O

Page 9: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

ATP

- energy

- Structure of Nucleic acides

- signal molecule

Page 10: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Macromolecules

- sugars -saccharides

- lipids

- proteins

- nucleic acids

Page 11: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Sugars - saccharides

Monosaccharides

- pentose – ribose, deoxyribose- hexose – glucose, fructose, galactose

Page 12: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

disascharides- saccharum, maltose, lactose

Sugars - saccharides

Page 13: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Polysaccharides - starch, glycogen, cellulose

Sugars - saccharides

glucose

glucogen

Page 14: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Proteins

Page 15: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Proteins

Page 16: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

biogenic amino acids, names a codes

Proteins

Aspartic Acid Asp D Glutamic Acid Glu E Phenylanine Phe F Glycine Gly G Alanine Ala A Cystine Cys C Histidine His H Isoleucine Ile I Lysine Lys K Leucine Leu L Methionine Met M Asparagine Asn N Proline Pro P Glutamine Gln Q Arginine Arg R Serine Ser S Threonine Thr T Valine Val VTryptophan Trp W Tyrosine Tyr Y

Page 17: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Amino acids

Page 18: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Amino acids sequence

3-D structure

Function of protein

Page 19: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Geneticcode

Page 20: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Peptide bond

Proteins

Page 21: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Proteins

Page 22: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace
Page 23: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace
Page 24: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace
Page 25: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace
Page 26: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace
Page 27: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Folding of proteins

Page 28: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Amino Acid Sequence

3-D Structure

Protein Function

Page 29: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace
Page 30: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

α, β−Helix pleadted sheet

Page 31: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

3-D structure of proteins1. Primary structure – amino acids sequence

(determine by mRNA)

2. secondary – α-or β-helix; pleated sheet(H-bonds)

3. Tertiary – 3-D protein structure(S-S bonds)

4. Quaternary – the final structure of proteins(subunits, prostetic units and etc.)

Page 32: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace
Page 33: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

3-D Structure of

proteins

Page 34: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Three ways of proteins bonds

Page 35: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Proteins are hungry

Page 36: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Amino Acid Sequence

3-D Structure

Protein Function

Page 37: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace
Page 38: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Nucleic acids

DNA-RNA

Page 39: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Nucleic acids

DNA

Page 40: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

ChromosomeNucleus consists one or more molecules DNA organized intochromosomes

Human: – 22 pars autozomes– 1 par sex chromosome

Human karyotypes

Page 41: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Human and mouse chromosomes:

Page 42: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

DNA chemical structure

Page 43: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace
Page 44: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Double helix of DNA

Page 45: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Double helix• Two complementary DNA strains

• Spring will be 52th anniversary of its discovery

Page 46: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace
Page 47: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace
Page 48: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Detection of DNA

Page 49: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Detection of DNA

Page 50: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Red – increase of sample transcripts

Green – increase of sample transcripts

Yellow – equal abundance

Limit of Detection: 1 in 30,000 transcripts

~ 20 transcripts/cell

Page 51: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Affymetrix GeneChip®

Limits: 1: 100,000 transcripts

~ 5 transcripts/cell

Affymetrix GeneChip®

Page 52: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Nuclear membraneChromatin fiber

} Other Chromatinfactors

H1

H1

Nuclear matrix

Nuclear pore

Nucleosomes

DNA

Chromatin fiber(30 nm dia.)

3-D Structure of DNA in nucleus

Page 53: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

DNA-protein complex

Page 54: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

DNAfolding

Page 55: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Chromatin structure

Page 56: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

DNA is wrapped around histone proteins as chromatinChromatin structure

Page 57: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace
Page 58: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

The Obstacles are Regulated: Histone Modifications

A Histone Code?

ChromoDomain

BromoDomain

• regulation of transcription • complex of genes to the DNA locus• protection of specific genes

Page 59: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

All cells – the same DNA- different reading of DNA- differentiation of cells

Page 60: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Histones play Key role in Regulation ofgene expression

Page 61: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Transcription and Processing

PolyA+RNA in red(a spliceosomal component) in green Overlap (red + green) = yellow

DNA in bluePolyA+RNA in red

Page 62: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

RNA• Ribonucleic

• Similar as DNA

• Tymine (T) is substituted by uracile (U)

• RNA can be:– One-strain helix– Double – strains helix– Hybridisated with DNA

Page 63: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

RNA• RNA is usually one strain

• It forms the 3-D secondary and tertiary structure

• The most important is extreme variability of the RNA molecules -sequence

Page 64: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

tRNA: sequence, 3-D structure

Page 65: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

mRNA• Messenger RNA

• Linear molecule coded genetic information – copy from DNA

• Transcription: process of copy mRNA from DNA

Page 66: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

mRNA modification• Eukaryotic genes are built:

• Exons: coding regions• Introns: non-coding regions

• splicing: cut of introns from molecule of mRNA and link the exons

• After this modification of mRNA is translated to sequence of protein

Page 67: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

mRNA modification

Image source: http://departments.oxy.edu/biology/Stillman/bi221/111300/processing_of_hnrnas.htm

Page 68: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

tRNA• Transfer RNA

• Precise 3-D structure

• The translation process of protein

Page 69: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

tRNA structure

Page 70: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

tRNA• Specific tRNA for each amino acid

• Determine by 3 nucleotide - anticodone(complementary with mRNA)

• Translation: process of prescription of codons of mRNA to sequence of amino acids to protein

Page 71: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

tRNA

Page 72: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

tRNA: sequence, 3-D structure

Page 73: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

tRNA structure

Page 74: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

rRNAsecondarystructure

Page 75: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

16S ribosomal RNA

Page 76: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

T. thermophilus - Ramakrishnan et al., Cell, 2002

Page 77: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Lipids

Page 78: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Schematic Diagram of a phospholipid molecule

(phosphatidylcholine)

Page 79: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Phospholipids

• Membranes of mammalian cells contain 3 major phospholipids– Classified according to the polar

headgroup

Page 80: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Saturated fatty acid

Unsaturated fatty acid

Differences in the length and degree of saturation of fatty acids affect their

ability to pack& hence the fluidity

of the bilayer

Choline head-group

Polar

Nonpolar

Phosphatidylcholine

Page 81: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace
Page 82: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Amphipathic

A, formula

B, schematic drawing

C, space-filling model

Page 83: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Cholesterol is oriented in the membrane between phospholipidmolecules with its polar end towards the outside surface of the monolayer and its hydrophobic end projecting into the interior of the membrane

Page 84: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace
Page 85: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace

Lodish et al, Fig 5-30

Page 86: Prezentace aplikace PowerPoint - Comenius University · PDF file3-D Structure Protein Function. ... sequence of protein. mRNA modification ... Lodish et al, Fig 5-30. Title: Prezentace