Protein Structure and Function
Proteins
• Make up about 15% of the cell
• Have many functions in the cell
– Enzymes, Structural, Transport, Motor, Storage, Signaling, Receptors, Gene regulation, Special functions
Shape = Amino Acid Sequence
• Proteins are made of 20 amino acids linked by peptide bonds
• Polypeptide backbone is the repeating sequence of the N-C-C-N-C-C… in the peptide bond
• The side chain or R group is not part of the backbone or the peptide bond
Protein Folding
• The peptide bond allows for rotation around it and therefore the protein can fold and orient the R groups in favorable positions
• Weak non-covalent interactions will hold the protein in its functional shape – these are weak and will take many to hold the shape
Non-covalent Bonds in Proteins
Globular Proteins
• The side chains will help determine the conformation in an aqueous solution
Hydrogen Bonds in Proteins
H-bonds form between 1) atoms involved in the peptide bond; 2) peptide bond atoms and R groups; 3) R groups
Protein Folding
• Proteins shape is determined by the sequence of the amino acids
• The final shape is called the conformation and has the lowest free energy possible
• Denaturation is the process of unfolding the protein
– Can be down with heat, pH or chemical compounds
– In the chemical compound, can remove and have the protein renature or refold
Refolding
• Molecular chaperones are small proteins that help guide the folding and can help keep the new protein from associating with the wrong partner
Protein Folding
• 2 regular folding patterns have been identified – formed between the bonds of the peptide backbone
• a-helix – protein turns like a spiral – fibrous proteins (hair, nails, horns)
• b-sheet – protein folds back on itself as in a ribbon –globular protein
b Sheets
• Core of many proteins is the b sheet
• Form rigid structures with the H-bond
• Can be of 2 types: Anti-parallel – run in an opposite direction of its neighbor (A)
– Parallel – run in the same direction with longer looping sections between them (B)
a Helix
• Formed by a H-bond between every 4th peptide bond – C=O to N-H
• Usually in proteins that span a membrane
• The a helix can either coil to the right or the left
• Can also coil around each other – coiled-coil shape – a framework for structural proteins such as nails and skin
Levels of Organization
• Primary structure : Amino acid sequence of the protein
• Secondary structure: H bonds in the peptide chain backbone
• a-helix and b-sheets
• Tertiary structure : Non-covalent interactions between the R groups within the protein
• Quaternary structure: Interaction between 2 polypeptide chains
Protein Structure
Domains
• A domain is a basic structural unit of a protein structure – distinct from those that make up the conformations
• Part of protein that can fold into a stable structure independently
• Different domains can impart different functions to proteins
• Proteins can have one to many domains depending on protein size
Useful Proteins
• There are thousands and thousands of different combinations of amino acids that can make up proteins and that would increase if each one had multiple shapes
• Proteins usually have only one useful conformation because otherwise it would not be efficient use of the energy available to the system
• Natural selection has eliminated proteins that do not perform a specific function in the cell
Protein Families
• Have similarities in amino acid sequence and 3-D structure
• Have similar functions such as breakdown proteins but do it differently
Proteins – Multiple Peptides
• Non-covalent bonds can form interactions between individual polypeptide chains
– Binding site – where proteins interact with one another
– Subunit – each polypeptide chain of large protein
– Dimer – protein made of 2 subunits
• Can be same subunit or different subunits
Single Subunit Proteins
Different Subunit Proteins
• Hemoglobin : 2 a globin subunits & 2 b globin subunits
Protein Assemblies
• Proteins can form very large assemblies
• Can form long chains if the protein has 2 binding sites – link together as a helix or a ring
• Actin fibers in muscles and cytoskeleton – is made from thousands of actin molecules as a helical fiber
Types of Proteins
• Globular Proteins – most of what we have dealt with so far
– Compact shape like a ball with irregular surfaces
– Enzymes are globular
• Fibrous Proteins – usually span a long distance in the cell
– 3-D structure is usually long and rod shaped
Important Fibrous Proteins
• Intermediate filaments of the cytoskeleton
– Structural scaffold inside the cell
• Keratin in hair, horns and nails
• Extracellular matrix
– Bind cells together to make tissues
– Secreted from cells and assemble in long fibers
• Collagen – fiber with a glycine every third amino acid in the protein
• Elastin – unstructured fibers that gives tissue an elastic characteristic
Collagen and Elastin
Stabilizing Cross-Links
• Cross linkages can be between 2 parts of a protein or between 2 subunits
• Disulfide bonds (S-S) form between adjacent -SH groups on the amino acid cysteine
Proteins at Work
• The conformation of a protein gives it a unique function
• To work proteins must interact with other molecules, usually 1 or a few molecules from the thousands to 1 protein
• Ligand – the molecule that a protein can bind
• Binding site – part of the protein that interacts with the ligand
– Consists of a cavity formed by a specific arrangement of amino acids