Chapter 3 Proteins

You Must Know How the sequence and subcomponents of proteins determine their properties. The cellular functions of proteins. (Brief – we will come back to this in other chapters.) The four structural levels of proteins and how changes at any level can affect the activity of the protein. How proteins reach their final shape (conformation), the denaturing impact that heat and pH can have on protein structure, and how these may affect the organism. The directionality of proteins (the amino and carboxyl ends).

Proteins account for more than 50% of the dry mass of most cells. Concept 3.5: Proteins include a diversity of structures, resulting in a wide range of functions Proteins account for more than 50% of the dry mass of most cells. Protein functions include defense, storage, transport, cellular communication, movement, and structural support. © 2014 Pearson Education, Inc. 3

Life would not be possible without enzymes. Enzymatic proteins act as catalysts, to speed up chemical reactions without being consumed by the reaction Enzyme © 2014 Pearson Education, Inc. 4

Polypeptides are unbranched polymers built from the same set of 20 amino acids A protein is a biologically functional molecule that consists of one or more polypeptides © 2014 Pearson Education, Inc. 5

Amino Acids: the monomers of proteins Figure 3.UN04 Amino Acids: the monomers of proteins Side chain (R group)  carbon Amino acids are organic molecules with carboxyl and amino groups. Amino acids differ in their properties due to differing side chains, called R groups. Amino group Carboxyl group 6

What do the side chains of these amino acids have in common? Figure 3.17a What do the side chains of these amino acids have in common? Side chain (R group) Glycine (Gly or G) Alanine (Ala or A) Valine (Val or V) Leucine (Leu or L) Isoleucine (le or ) Nonpolar side chains; hydrophobic Methionine (Met or M) Phenylalanine (Phe or F) Tryptophan (Trp or W) Proline (Pro or P) 7

What do the side chains of these amino acids have in common? Figure 3.17b What do the side chains of these amino acids have in common? Serine (Ser or S) Threonine (Thr or T) Cysteine (Cys or C) Figure 3.17b The 20 amino acids of proteins (part 2: polar) Polar side chains; hydrophilic Tyrosine (Tyr or Y) Asparagine (Asn or N) Glutamine (Gln or Q) 8

What do the side chains of these amino acids have in common? Figure 3.17c What do the side chains of these amino acids have in common? Aspartic acid (Asp or D) Glutamic acid (Glu or E) Figure 3.17c The 20 amino acids of proteins (part 3: charged) Electrically charged side chains; hydrophilic Acidic amino acids are those with side chains that are generally negative charge owing to the presence of a carboxyl group, which is usually ionized at cellular pH. 9

What do the side chains of these amino acids have in common? Figure 3.17c What do the side chains of these amino acids have in common? Arginine (Arg or R) Lysine (Lys or K) Histidine (His or H) Figure 3.17c The 20 amino acids of proteins (part 3: charged) Electrically charged side chains; hydrophilic Basic amino acids have amino groups in their side chains that are generally positive in charge. 10

You don’t need to memorize all the different side chains of the amino acids, but when shown a side chain you should be able to identify its properties (e.g. polar, ionized, etc.)

N-terminus peptide bond C-terminus Amino acids are linked by peptide bonds A polypeptide is a polymer of amino acids Polypeptides range in length from a few to more than a thousand monomers Each polypeptide has a unique linear sequence of amino acids, with a carboxyl end (C-terminus) and an amino end (N-terminus) Peptide bonds are formed by dehydration reactions, which link the carboxyl group of one amino group of the next.

Protein Structure and Function A functional protein consists of one or more polypeptides precisely twisted, folded, and coiled into a unique shape. A protein’s structure determines its function! Hemoglobin protein © 2014 Pearson Education, Inc. 13

How does an organism “know” what proteins to make? DNA dictates the sequence of amino acids. The sequence of amino acids leads to the protein’s three-dimensional structure.

Four Levels of Protein Structure Proteins are very diverse, but share three superimposed levels of structure called primary, secondary, and tertiary structure. A fourth level, quaternary structure, arises when a protein consists of more than one polypeptide chain © 2014 Pearson Education, Inc. 15

Primary structure of transthyretin Figure 3.21a Primary structure Amino acids 1 5 10 Amino end 30 25 20 15 35 40 45 50 Primary structure of transthyretin 55 70 65 60 The sequence of amino acids make up the primary structure of a protein. 75 80 85 90 95 115 110 105 100 120 125 Carboxyl end 16

Secondary structure  helix Hydrogen bond  pleated sheet  strand Figure 3.21ba Secondary structure  helix Hydrogen bond  pleated sheet  strand The secondary structure is the result of hydrogen bonds between the repeating constituents of the polypeptide backbone (not the amino acid side chains). Hydrogen bond 17

Tertiary structure Hydrogen bond Hydrophobic interactions and Figure 3.21d Tertiary structure Hydrogen bond Hydrophobic interactions and van der Waals interactions Disulfide bridge Ionic bond The tertiary structure is the overall shape of a polypeptide resulting from interactions between the side chains of the various amino acids. The disulfide bridge is a covalent bond that forms between sulfhydryl groups. Polypeptide backbone 18

Quaternary Structure Heme Iron  subunit  subunit  subunit  subunit Figure 3.21f Quaternary Structure Heme Iron  subunit  subunit Some proteins consist of two or more polypeptide chains aggregated into one functional macromolecule. Quaternary structure is the overall protein structure that results from the aggregation of these polypeptide subunits.  subunit  subunit Hemoglobin 19

“mad cow disease” You will not be tested on this material. “A prion (i/ˈpriːɒn/[1]) in the Scrapie form (PrPSc) is an infectious agent composed of protein in a misfolded form.[2] This is the central idea of the Prion Hypothesis, which remains debated.[3] This would be in contrast to all other known infectious agents, like viruses, bacteria, fungi or parasites—which must contain nucleic acids (either DNA, RNA, or both). The word prion, coined in 1982 by Stanley B. Prusiner, is derived from the words protein and infection.[4] Prions are responsible for the transmissible spongiform encephalopathies in a variety of mammals, including bovine spongiform encephalopathy (BSE, also known as "mad cow disease") in cattle. In humans, prions cause Creutzfeldt-Jakob Disease (CJD), variant Creutzfeldt-Jakob Disease (vCJD), Gerstmann–Sträussler–Scheinker syndrome, Fatal Familial Insomnia and kuru.[5] All known prion diseases in mammals affect the structure of the brain or other neural tissue and all are currently untreatable and universally fatal.[6] In 2013, a study revealed that 1 in 2,000 people in the United Kingdom might harbour the infectious prion protein that causes vCJD.[7] Prions are not considered living organisms but are misfolded protein molecules which may propagate by transmitting a misfolded protein state. If a prion enters a healthy organism, it induces existing, properly folded proteins to convert into the disease-associated, misfolded prion form; the prion acts as a template to guide the misfolding of more proteins into prion form. These newly formed prions can then go on to convert more proteins themselves; this triggers a chain reaction that produces large amounts of the prion form.[8] All known prions induce the formation of an amyloid fold, in which the protein polymerises into an aggregate consisting of tightly packed beta sheets.” From http://en.wikipedia.org/wiki/Prion

In addition to primary structure, physical and chemical conditions can affect structure. Alterations in pH, salt concentration, temperature, or other environmental factors can cause a protein to unravel. This loss of a protein’s native structure is called denaturation. A denatured protein is biologically inactive. 21

Normal protein Figure 3.23-1 Figure 3.23-1 Denaturation and renaturation of a protein (step 1) Normal protein 22

Normal protein Denatured protein Figure 3.23-2 Figure 3.23-2 Denaturation and renaturation of a protein (step 2) Normal protein Denatured protein 23

Normal protein Denatured protein Figure 3.23-3 Figure 3.23-3 Denaturation and renaturation of a protein (step 3) Normal protein Denatured protein 24