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 4^th 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