Protein Structure and Function Chap.

Part I Hierarchical Structure of Proteins

Primary Structure

N-term.

C-term.

Secondary Structure-alpha (a) helix

Secondary Structure-beta () sheet

Tertiary Structure

Motifs-Regular Combinations of Secondary Structure

Motifs-Regular Combinations of Secondary Structure

Motifs-Regular Combinations of Secondary Structure

Protein Domains

3 Structure of HA

Modular Nature of Proteins

Quaternary Structure of Proteins

Macromolecular Assemblies

Transcription Initiation Machinery

Conservation of Protein Structure and Function Throughout Evolution

Structural Similarities of the Different Globins

Part II Folding, Modification, and Degradation of Proteins

Molecular Chaperone-Mediated Protein Folding

1. ATP-bound Hsp70 binds to unfolded protein 2. Hydrolysis of ATP to ADP (release of Pi) promotes folding 3. Exchange of ATP for ADP releases folded protein

Chaperonin Mediated Protein Folding

Chemical Modification of Amino Acid Residues

Chemical Modification of Amino Acid Residues

Protein Degradation
-Protein Life span varies from a few minutes to the life of the cell -Several pathways for degradation of proteins

Protein Degradation
-Protein Life span varies from a few minutes to the life of the cell -Several pathways for degradation of proteins 1. Lysosomal-membrane bound organelle -Interior is highly acidic and contains hydrolytic enzymes -Primarily degrade extracellular proteins taken up by the cell

Pathways for Lysosomal Degradation of Proteins

Fig. 5-20

Protein Degradation
-Protein Life span varies from a few minutes to the life of the cell -Several pathways for degradation of proteins 1. Lysosomal-membrane bound organelle -Interior is highly acidic and contains hydrolytic enzymes -Primarily degrade extracellular proteins taken up by the cell 2. Proteasome-directed degradation-Macromolecular machine that degrades proteins than have been poly-ubiquitinated -Ubiquitin-76 amino acid polypeptide that is covalentely attached to lysine residues -Polyubiquitin chain is recognized by the proteasome -Degrades proteins in an ATP-dependent manner into short (7-8 amino acid) peptides

Ubiquitination and Proteasome-mediated Protein Degradation

Part III Enzymes and Chemical Work of Cells

Antibody-Antigen Interactions are Highly Specific

Antibody-Antigen Interactions are Highly Specific

Enzymes
-Catalyze chemical alteration of their ligands -Ligand=Substrate -Most chemical reactions in the cell are catalyzed by enzymes -Enzymes do not alter the reaction -Enzymes increase the reaction rate by lowering the activation energy i.e.-accelerate the formation of products from reactants without altering the value of G

Enzymes Accelerate the Reaction Rate

Enzyme Active Site Binds the Substrate

Protein Kinase A (PKA)

Kinase Core240 Amino acid domain of PKA

Conformational Change Caused by Substrate Binding

No Substrate bound

Substrate binding causes conformational change to bring ATP and peptide binding sites closer together

Enzyme Kinetics
-Conversion of one substrate into a product using two different enzyme concentrations and increasing substrate concentrations

Enzyme Kinetics
-Conversion of one substrate into a product using constant enzyme concentration and two substrates -Enzyme has different affinity for the two substrates

Enzymes in Common Pathways

Diffusion of product to next enzyme in the pathway

Scaffold-keeps enzymes close to each other

Multifunctional Enzyme-enzyme encoded by a single gene that has more than one catalytic activity

Pyruvate Dehydrogenase Complex

Part IV

Mechanisms for Regulating Protein Function

Cooperative Binding of O2 to Hemoglobin

Ligand Binding Activates Protein Kinase A Catalytic Subunit

Calmodulin Functions as Ca2+ Binding Switch Protein

GTP-Binding Proteins Function as Molecular Switches

Regulation of Protein Function by Phosphorylation/Dephosphorylation