PROTEINS. Amino acids are the building blocks of proteins. Acid L-form * * Lecture 6 Macromolecules #2 O = N -C -C-O.

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1 Proteins: Linear polymers of amino acids workhorses of the cell tools, machines & scaffolds Lecture 6 Macromolecules #2 PRTEINS 1 Enzymes catalysts that mediate reactions, increase reaction rate Structural roles scaffolds, skeleton; mechanical support Motility motors & generators; contractile elements Regulate control & coordinate; hormones, growth factors, gene activators Facilitate transport through membranes; what enters, what leaves 2 PRTEINS are consist of one or more Polypeptides Polypeptides are polymers of AMIN ACIDS Amino acids are the building blocks of proteins R N C C * * Amine Carboxylic Acid Lform * * Dform Always an 3 4

2 Monomers: 20 Lamino L acids are used to synthesize proteins Amino acids differ by what their Rgroup R is 20 different types of R groups NonPolar il hydrocarbon Same chassis, different bodies Polar S C Charged N 3 nonpolar aliphatic aromatic uncharged polar Charged: acidic basic 5 Polar Cysteine Forms Disulfide bridges 9V Energizer 6 Amino acids with nonpolar Rgroups (hydrophobic) Isoleucine (Ile) Amino acids with uncharged, polar R groups (hydrophilic) Glycine (Gly) Alanine (Ala) Valine (Val) Leucine (Leu) ethionine (Met) Phenylalanine (Phe) Tryptophan (Trp) Proline (Pro) 7 Serine (Ser) Threonine (Thr) Cysteine (Cys) Tyrosine (Tyr) Asparagine (Asn) Glutamine (Gln) 8

3 mino acids with charged R groups hydrophilic): acidic basic The amino and acid groups couple the monomers together R 1 R 2 R 3 spartate (Asp) Aspartic acid acidic side chains () charged at p 7 Glutamate (Glu) Glutamic acid Lysine (Lys) Arginine (Arg) basic side chains charged at p 7 istidine (ys) 9 R 1 R 2 R 3 Can make polymers which are 100 s to 1000 s of amino acids long Can KEEP adding on to the end 10 A special type of Dehydration Synthesis R 1 N C C R 1 R 2 N CCN CC PEPTIDE Bond R 2 N C C Polypeptide Chain 11 water Formation of peptide bonds: another condensation dehydration rxn Requires energy & information! 12

4 Amino Acid Polymers Peptide bond S C 2 C 2 C 2 C C N C C N C C DESMSMES N Individual Polypeptides (Proteins) Differ by: Length Proportion Sequence total number amino acids in polymer abundance of particular amino acids the particular RDER of amino acids DESMSMES DESMSMES (a) S Peptide C 2 C 2 bond C 2 2 Side chains Primary Structure Met Ala Cys Glu Ser Thr Val Val Leu Cys Arg NP NP P P P NP NP NP P hook hook N C C N C C N C C Backbone Figure 5.18 (b) Amino end (Nterminus) Carboxyl end (Cterminus) Proteins have 4 levels of organization 1 o (primary) amino acid sequence 2 o (secondary) local folding of backbone 3 o (tertiary) overall 3D folding of polypeptide 4 o (quaternary) two or more polypeptides 15 Secondary Structure: local folding stabilized by polar peptide bonds hydrogen bonding to other peptide bonds further up the chain R 1 N CCN CC N CC N Etc. R 2 PLAR Polypeptide Chain R 3 16

5 lypeptide Chain Polypeptide Chain YDRGEN BNDING PLAR PLAR 17 4 common types of secondary s: α helix β sheet organized turn random coil 18 The polypeptide backbone hydrogen bonds to form a repeating coil α helix 19 Rgroups 20

6 β sheet The polypeptide backbone hydrogen bonds to backbone on adjacent polypeptide (segment) to form a sheet Both Alpha helix and Beta Sheet Present Surfaces of their Rgroups with backbone tucked inside rganized Turn Random Coil fuzzy can shag carpet Rigid 23 Flexible 24

7 3 o Tertiary Structure: depends ~ entirely on interactions of R groups he 3D of the entire polypeptide Salt Bridges and ydrogen bonding Also stabilize tertiary s ertiary Structure ne stabilizing force is hydrophobic interactions 27 28

8 31 32 ydrophobic residues on inside Polar residues on outside surface Charge interactions Coordinating and Stabilizing domain/arm positions Disulfide Bridges between cysteine residues N C C C 22 3 C C 3 yrdogen 3 C C 3 bond C C C 2 C 2 S S C 2 Disulfide bridge C 2 N 3 C C 2 Ionic bond ydrophobic interactions and van der Waals interactions C Polypeptide backbone 29 Disulfide bonds are CVALENT & help maintain tertiary 30 2º s combine to form common structural motifs

9 Domains modular units of function emoglobin Quaternary Structure interaction of MRE TAN 1 Polypeptide Chain to Form a Functional Protein For example 4 subunits 4 polypeptides GAPD 2 domains 2 different functions 33 NE PRTEIN Note: many proteins functional as a just single polypeptide 34 4 Quaternary Structure Applies only to proteins with >1 polypeptide chain Stabilized by same forces that stabilize 3 : interaction of hydrophobic surfaces hydrogen bonding between Rgroups electrostatic (ionic) interactions between Rgroups disulfide bridges between Rgroup cys residues (covalent bonds) 35 Sicklecell disease Results from a single amino acid substitution in the protein hemoglobin Normal Sicklecell Primary hemoglobin Primary hemoglobin Val is Leu Thr Pro Glul Glu... Val is Leu Thr Pro Val Glu Secondary Secondary and tertiary β subunit and tertiary β subunit s s α β Quaternary emoglobin A Quaternary α β α β α β Function Function Molecules do not associate with one another, each carries oxygen. 10 µm 10 µm Red blood Normal cells are cell shape full of individual Red blood hemoglobin cell shape molecules, each carrying oxygen Figure 5.21 Exposed hydrophobic region emoglobin S Molecules interact with one another to crystallize into a fiber, capacity to carry oxygen is greatly reduced. Fibers of abnorma hemoglobin deform cell into sickle shape. 36

10 Protein misfolding can be deadly kuru CreutzfeldJakob disease madcow disease Prions Summary Proteins, polypeptides Peptide bond Amino acid types 20 Primary peptide bond Secondary Structure backbone bonds Tertiary Structure Rgroup interactions Quaternary Structure Rgroup interactions PrP c PrP Sc 37 38