Chapter 4 Protein Structure PDF

Chapter 4 Protein Three- Dimensional Structure  Learning Objectives Be able to describe the features of the four levels of protein structure: Primary structure Secondary structure Tertiary structure Quaternary structure Be able to describe the relation...

Chapter 4 Protein Three- Dimensional Structure  Learning Objectives Be able to describe the features of the four levels of protein structure: Primary structure Secondary structure Tertiary structure Quaternary structure Be able to describe the relationship between the structure and function of a protein.  4.1 Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains Primary Structure – linear strand of amino acids Peptide bonds link carboxylic acid of one amino acid to the amino group of the next amino acid Formation of the bond is a dehydration synthesis reaction Loss of a water molecule Synthesis of peptide bonds requires energy input Very stable bonds Polypeptide chain – chain of amino acids Has directionality or polarity Amino group on one end of chain – beginning Amino-terminal (N-terminal) Carboxyl group on the other end of chain – end Carboxyl-terminal (C-terminal) Figure 4.1, Page 50 Figure 4.2, Page 50  4.1 Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Polypeptide Chain Chains Main chain or backbone – regularly repeating portion Amino group, α carbon with hydrogen, and carboxyl group Carboxyl group is a good hydrogen-bond acceptor Amino group is a good hydrogen-bond donor Side chain – variable portion R group Hydrogen bonding between carboxyl groups and amino groups of the main chain or side chains help to stabilize particular structures Figure 4.3, Page 51  4.1 Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains Proteins – typically 50-2000 amino acids or more Oligopeptides (peptides) - < 50 amino acids Covalent cross-linkages within or between polypeptide chains Disulfide bonds – oxidation between two cysteine residues Loss of electrons Figure 4.4, Page 51  4.1 Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains Knowing amino acid sequences is important for: 1. Determining the three-dimensional structure of a protein 2. Knowing the function of the protein 3. Understanding abnormal function and diseases that result from changes in the sequence 4. Understanding its evolutionary history  4.1 Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains Polypeptide Chains Are Flexible Yet Conformationally Restricted Peptide bond is essentially planar Six atoms in the same plane: α-carbon atom and CO group of first amino acid NH group and α-carbon atom of second amino acid Peptide bond has considerable double bond character Electrons resonate between pure single bond and pure double bond Distance of peptide bond is between that of a single bond and double bond between carbon and nitrogen Peptide bond is uncharged Allow for formation of globular structures that would not be able to occur if charges repelled each other Figure 4.6, Page 52 Unnumbered Art, Page 52  4.1 Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains Polypeptide Chains Are Flexible Yet Conformationally Restricted Within an amino acid, the bonds between the amino group and α-carbon and the α-carbon and carboxyl group are pure single bonds The rigid peptide bonds can rotate around these bonds This freedom of rotation allows proteins to fold in many different ways Figure 4.9, Page 53  4.2 Secondary Structure: Polypeptide Chains Can Fold into Regular Structures Secondary Structures Alpha helices Beta pleated sheets Turns Loops Formed by regular patterns of hydrogen bonds that form between NH and CO groups of amino acids near each other in primary structure  4.2 Secondary Structure: Polypeptide Chains Can Fold into Regular Structures The Alpha Helix Is a Coiled Structure Stabilized by Intrachain Hydrogen Bonds Rodlike structure with a tightly coiled backbone Side chains extend out away from backbone Hydrogen bonds form between NH and CO groups of amino acids of main chain CO hydrogen bonds to NH 4 amino acids in front of it Only amino acids near ends of helix are not hydrogen bonded 3.6 amino acids per turn of helix Amino acids that branch at β-carbon atom destabilize alpha helices Valine, threonine, and isoleucine Amino acids that have side chains with hydrogen-bond acceptors or donors near the main chain destabilize alpha chains Serine, aspartate, and asparagine Proline destabilizes alpha helices because lacks NH group and ring doesn’t fit into helix  4.2 Secondary Structure: Polypeptide Chains Can Fold into Regular Structures Beta Sheets Are Stabilized by Hydrogen Bonding Between Polypeptide Strands Two or more polypeptide strands called β strands that are fully extended and linked together by hydrogen bonds Antiparallel β sheet – strands run in opposite directions Parallel β sheet – strands run in same direction Side chains of adjacent amino acids point in opposite directions 4-5, but up to 10, β strands per β sheet All antiparallel, all parallel, or mixed within one β sheet Portions of polypeptide chain can be at distant sections Depicted using broad arrows that point toward carboxyl-terminal end Can be flat or twisted in shape  4.2 Secondary Structure: Polypeptide Chains Can Fold into Regular Structures Polypeptide Chains Can Change Direction by Making Reverse Turns and Loops Turns and loops are found on the surface of the protein Interact with other proteins or the environment  4.3 Tertiary Structure: Water- Soluble Proteins Fold into Compact Structures Tertiary Structure Spatial arrangement of amino acids that are far apart in the sequence Pattern of disulfide bonds Interactions between side chains Protein folding is driven by the hydrophobic effect Folds so hydrophobic side chains are buried in the interior of the protein Polar, charged side chains are on the surface of the protein Interact with aqueous environment inside cells Interior of protein has main chains that form secondary structures Van der Waals interactions occur between hydrophobic side chains to increase protein stability  4.4 Quaternary Structure: Multiple Polypeptide Chains Can Assemble into a Single Protein Quaternary Structure Arrangement of subunits and nature of their interactions Subunit – single polypeptide chain Subunits interact via weak interactions Hydrogen bonding, ionic bonding, and van der Waals interactions Can be made up of identical subunits or different subunits Can vary in number as well 4.5 The Amino Acid Sequence of a Protein Determines Its Three- Dimensional Structure Denatured proteins – proteins that have lost their normal shape and thus function Under specific conditions, proteins can refold properly and become active again Others are not able to refold without assistance of chaperones Central Principle of Biochemistry Sequence specific conformation Conformation determines function