Chemical agents PROTEINS: The Molecular Tools of the Cell Polypeptide Chains: Polymers of amino acids that are arranged in a specific linear sequence and are linked by peptide bonds Protein: A macromolecule which consists of one or more polypeptide chains folded and coiled into specific conformations.

: PROTEINS Are abundant: 50% 0f a cell’s dry weight Have these important functions: Structural support Storage of amino acids Transport (hemoglobin) Signaling (chemical messengers) Cellular response to chemical stimuli (receptor molecules) Movement (contractile proteins) Defense against antigens (antibodies) Catalysis of biochemical reactions (enzymes)

MORE PROTEINS: Vary extensively in structure: Every one has its own unique 3-D shape (conformation) They are made of only amino acid monomers 20

POLYPEPTIDES: Polymers of amino acids connected in a specific sequence. AMINO ACIDS: Building blocks of proteins: consisting of an asymmetric carbon (Alpha Carbon) which is covalently bonded to a H atom Carboxyl group Amino group Variable (R) Group

AMINO ACID:

Amino Acid Classification: Those With: POLAR SIDE GROUPS: Hydrophilic Can be uncharged polar or…. Charged polar: These can have… Acidic side groups (dissociated COOH are Neg.) Basic side groups (Amino group has an extra H+) NONPOLAR SIDE GROUPS: Hydrophobic

POLYPEPTIDE CHAINS Polymers formed when amino acids are joined with PEPTIDE BONDS: Covalent bonds formed by a condensation reaction that links a COOH of one amino with the Amino Group of the other. These have polarity These have a –N-C-C-N-C-C- backbone Range from a few monomers to a few 1000 Have unique linear sequences

PEPTIDE BONDS

A Protein’s Function Depends on its Specific Conformation PROTEIN CONFORMATION: 3 Dimensional Shape of a Protein NATIVE CONFORMATION: Functional conformation of a protein found under normal biological conditions.

CONFORMATIONS: Enables a protein to recognize/bind specifically to another molecule (hormone/receptor, enzyme/substrate, antibody/antigen) Caused by a specific linear sequence of amino acids Is produced when a newly formed polypeptide chain coils and folds spontaneously, mostly due to hydrophobic interactions Is stabilized by chemical bonds/weak interactions between neighboring regions of the folded protein

FOUR LEVELS OF PROTEIN STRUCTURE Primary Structure Secondary Structure Tertiary Structure Quaternary Structure (2 or more polypeptide chains)

PRIMARY STRUCTURE Unique Sequence of Amino Acids in a Protein Determined by genes A slight change can affect conformation and function (sickle cell anemia) Can be sequenced in the lab (Frederick Sanger)

SECONDARY STRUCTURE Regular, repeated coiling and folding of a polypeptide’s backbone (Campbell 5.20) Contributes to a protein’s overall conformation Stabilized by H bonds between peptide linkages in the protein’s “backbone” (Carbonyl and amino groups) Alpha Helices and Beta sheets are the 2 major types

SECONDARY: ALPHA HELIX Secondary Structure: A helical Coil stabilized by H bonding between every fourth peptide bond Described by Linus Pauling and Robert Corey in ’51 Found in fibrous proteins like keratin and collagen)

SECONDARY: BETA (PLEATED) SHEETS Secondary protein structure which is a sheet of antiparallel chains folded into accordian pleats. Parallel regions are held together bt interchain or intrachain H bonds between adjacent polypeptides Make up the dense core of many globular proteins, and a major portion of some fibrous ones

TERTIARY STRUCTURE: The 3 dimensional shape of a protein. The irregular shapes are due to bonding between the side chains and interactions of the side chains and the aqueous environment Can be weak interactions: H bonding between side chains Ionic bonding between side chains Hydrophobic interactions between nonpolar side chains in protein’s interior

TERTIARY STRUCTURE: Can contain covalent linkages: Disulfide Bridges form between 2 cysteine monomers brought together by the folding of the protein

DISULFIDE BRIDGES

QUATERNARY STRUCTURE Structure that results from the interactions between and among several polypeptide chains (Campbell 5.23) Collagen:Fibrous protein w/3helices supercoiled into a triple helix:VERY STRONG: Animal connective tissue Hemoglobin: 2 alpha chains, 2 beta chains fit tightly together

What Determines Protein Conformation Influenced by physical and chemical interactions Can be denatured if: Transferred to an organic solvent Chemical agents disrupt H bonds Chemical agents disrupt ionic bonds Chemical agents disrupt disulfide bridges Excessive heat is applied to the protein

The Protein Folding Problem: Hard to predict…….. Most proteins pass through intermediate stages, we can’t always see these, and can’t tell just by looking at the final conformation The native conformation can be dynamic: alternating between several shapes CLUES: We can now track a protein through its intermediate stages CHAPERONE PROTEINS have been discovered which temporarily brace a folding protein