Levels of Protein Structure

Why is the structure of proteins (and the other organic nutrients) important to learn?

Protein Structure - Introduction The multiplicity of functions performed by proteins arises from the huge number of different 3D shapes they adopt: function follows structure; function is determined by structure Proteins are the most structurally complex and functionally sophisticated molecules known

Review Amino acids are the subunits (monomers, building blocks) of proteins Defining property: all have a carboxyl (COOH) (carboxylic acid) group and an amino group (NH 2 ) bonded to the alpha carbon Amino acids in a sequence are also called residues

Review The bond that forms between two amino acids is called the peptide bond –Formed between the carbon of the carboxyl group on one amino acid and the nitrogen of the amino group on the adjacent amino acid –**This bond is covalent There are twenty standard amino acids found in proteins –Bacteria, plants, animals

Polypeptide Backbone The backbone of proteins (remember: also called polypeptides) consists of repeating sequence of atoms N-C-C-N-C-C-N-C-C-N… Only the alpha Carbon, Nitrogen of the amino group, and Carbon of carboxyl group is considered in the backbone

R Groups/Radical/Variant/ Side Chains The chemical versatility of the R group of amino acids is vital to the function of proteins R groups are also called side chains –They are not involved in peptide bonding but are what give each amino acid its unique properties

Quick chem: Electronegativity Polarity is caused by the electronegativity of atoms: the tendency of an atom in a bond to attract electrons towards itself. Highly electronegative atoms are, in order: F > O > N > Cl Carbon and hydrogen have similar electronegativities so the CH bond is not polarized.

Quick Chem: Polar vs. Nonpolar Polar bond: when electrons are not shared equally between atoms in a molecule Nonpolar: electrons are shared

Quick Chem: Hydrogen Bonding When a bond forms between an electronegative atom, usually Oxygen or Nitrogen, and a hydrogen bonded to another electronegative atom These bonds can occur between two molecules (like water) or within the same molecule (like DNA and like you will see with proteins…)

Level 1: Primary Structure a.k.a Amino Acid Sequence or Primary Sequence The primary structure of a protein is simply the order in which the amino acids that make up the protein are in –The sequence of aa in a protein “The one dimensional first step in specifying the three dimensional structure of the protein”  –All of the information required for a polypeptide chain to fold is contained in its amino acid sequence

Example of Primary Structure Gelatin: Ala-Gly-Pro-Arg-Gly-Glu-4Hyp-Gly-Pro

Primary Structure Each of the thousands of known proteins has its own particular amino acid sequence Because each aa ca be used many times, and there is no length restriction, the possible number of combinations is HUGE

Level 2: Secondary Structure Secondary structures have repetitive patterns caused by the hydrogen bonding So it’s one part of the backbone being attracted to another part of the backbone –Side chains are NOT part of the secondary structure

Common Secondary Structure: The Alpha Helix Alpha Helix: in which every backbone N-H group hydrogen bonds to the backbone C=O group of the amino acid four residues earlier

Common Secondary Structure: Beta Sheet Hydrogen bonding between the backbone carbonyl (C=O) of an amino acid in one strand and the backbone amide N-H of a second amino acid in another strand

Secondary Structure Many regions of different secondary structure can be present in the same protein molecules

Primary and Secondary Structure Primary structure: linear sequence of aa's Secondary structure: - regular, recurring folding of the protein backbone due to H-bonding

Importance of the Chemical Characteristics of the Side Chain The twenty amino acids found in proteins are classified based on the chemical characteristics of their side chains: polar/nonpolar, basic/ acidic, aromatic, positively charged/negatively charged

Tertiary Structure Arrangement of secondary structures + side chains

Protein Level 3: Tertiary Structure The tertiary structure is the final specific geometric shape that a protein assumes. This final shape is determined and stabilized by a variety of bonding interactions between the side chains of the amino acids These bonding interactions between side chains may cause a number of folds, bends, and loops in the protein chain; different fragments of the same chain may become bonded together.

Interactions Between Side Chains that Contribute to Tertiary Structure We will learn three types of bonding interactions between side chains including: hydrogen bonding, salt bridges, disulfide bonds; and the effect of polarity of side chains on structure

Ionic Bonds/Salt Bridges The reaction is simply the transfer of a H+ (positive ion); the attraction of the positive and negative charges; (ionic bonding). The interaction of the acid and base side chains; these are used in the salt formation.

Disulfide Bonding

Polarity of Side Chains A critical factor governing the folding of any protein is the distribution of its polar and nonpolar side chains Nonpolar side chains tend to be forced together in an aqueous environment; aggregate in interior of protein molecule Polar side chains arrange themselves near the outside of the molecule

Quaternary Structure The combination of two or more polypeptide chains forming one complete unit The interactions between the chains are not different from those in tertiary structure; are distinguished only by being interchain rather than intrachain

Tertiary Structure Three main classes of proteins correlate with typical tertiary structures: Globular: the polypeptide chain folds up into a compact shape like a ball with an irregular surface; water soluble Fibrous: relatively simple, elongated structure; insoluble in water Membrane proteins: insoluble; beta barrel, alpha helical,etc

Primary: sequence of amino acids in the protein Secondary: hydrogen bonding b/w backbone groups Tertiary: interactions of side chains Quaternary: two or more polypeptide chains

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“Cool” things about proteins Blood type is based on the proteins present in each Luminol detects blood proteins Antibiotics interfere with protein synthesis in bacteria

Application In a protein 146 aa long, a valine (hydrophobic R group) is substituted for a glutamic acid (acidic R group) at position 6. What is/are the effects of this substitution?