BIOL111 Lecture 8 Protein Structure and Function II (2018) AL.pdf

Tertiary structure For most proteins, the final three-dimensional structure of a protein is produced by the association of the secondary structures into compact domains. This is called TERTIARY STRUCTURE Unfolded polypeptide Formation of a helices and b sheets Correctly folded compact domains PR...

Tertiary structure For most proteins, the final three-dimensional structure of a protein is produced by the association of the secondary structures into compact domains. This is called TERTIARY STRUCTURE Unfolded polypeptide Formation of a helices and b sheets Correctly folded compact domains PRIMARY STRUCTURE SECONDARY STRUCTURE TERTIARY STRUCTURE Non-covalent bonding in tertiary structure As in the formation of secondary structures, noncovalent bond are important for correct tertiary structure: • Ionic bonds • Hydrogen bonds • Van der Waals forces Disulphide bridges The side chain of one CYSTEINE can form a crosslink with the side chain of another which is near to it in space. This crosslink is called a DISULPHIDE BRIDGE, and is a covalent bond. Disulphide bridges make proteins more resistant to degradation and denaturation Diagrammatic representation of tertiary structure Because of the large number of atoms in a typical protein molecule, diagrams usually look very complex. Therefore, only the polypeptide backbone is usually shown drawn as a thick line or ribbon. The presence of an a-helix is usually indicated by the inclusion of a SPIRAL or CYLINDER within the ribbon. b-strands are drawn as thick ARROWS, pointing from the N-terminal end to the C-terminal. Quaternary structure Many proteins are formed from more than one polypeptide chain. Such proteins have QUATERNARY STRUCTURE The chains, SUBUNITS, associate into a MULTIMERIC COMPLEX which is held together by electrostatic, hydrogen and van der Waals bonds (and sometimes disulphide bridges) Homodimers and Heterodimers Haemoglobin I Antibodies Summary – four levels of protein structure I The primary structure of a protein is the sequence of amino acids which form the polypeptide chain and the position of any disulphide cross-links. This therefore represents all of the covalent bonds within the protein. Different regions of the polypeptide chain then fold into regular local secondary structures, e.g. a-helices and b-sheets. Tertiary structure is then formed by the packing of these structural elements into compact globular domains. Some proteins contain several subunits formed from individual polypeptides arranged in a quaternary structure. Summary – four levels of protein structure II Protein types There are two major classes of proteins: GLOBULAR Protein chain(s) are arranged in compact domains Usually active components of the cellular ‘machinery’ FIBROUS Protein chains are arranged into fibres Have a structural role There are three main groups of fibrous proteins defined by the secondary structure: coiled-coil (e.g. keratin and myosin) b-sheets (e.g. amyloid fibres and silks) triple helix (the collagens) α-Keratin I • The keratins are a family of mechanically durable proteins found in hair, nails, feathers, etc. • The primary structure of a-keratin has a 7 amino acid repeat, a-b-c-d-e-f-g, which forms an a-helix • Residues a and d are hydrophobic and lie on the same side of the a-helix; b, c, e, f, g can be any amino acid • Two a-keratin helices twist around each other, associating via the hydrophobic faces of the helices. This forms a COILED-COIL α-Keratin II The coiled-coil dimer then lines up with another to form a staggered antiparallel tetramer The tetramers are the building blocks of protofilaments which then form into protofibrils which then form microfibrils Fibroin I Produced by silkworms Long stretches of silk fibroin contain a six amino acid repeat (-Gly-Ser-Gly-Ala-Gly-Ala-)n which forms an antiparallel b-sheet The glycine side chains (H) project from one side of the sheet and those of serine (CH2OH) and alanine (CH3) project from the other. Fibroin II Silk is extremely strong as any stretching would require the breaking of covalent bonds, yet it is flexible because the bsheets are interacting via weak van der Waals bonds The b-sheets can stack into an array with layers of contacting Gly side chains alternating with layers of Ser/Ala side chains Collagen The most abundant vertebrate protein Forms strong fibres present in skin, bone, teeth, cartilage, etc. Nearly one-third of the amino acids are glycine. Another 15-30% are proline or hydroxyproline (Hyp) The primary amino acid sequence consists of a repeating tripeptide of Gly-X-Y where X is often Pro and Y is often Hyp Collagen cannot form an a-helix because of the Pro and Hyp residues. Instead it forms a ‘loose’ helix with around three residues per turn The collagen triple helix Three collagen polypeptides wind around each other in a rope-like twist to form a TRIPLE HELIX Every 3rd amino acid passes through the centre of the triple helix which is so crowded that only Gly can fit The Pro and Hyp residues confer rigidity The polypeptide chains form inter-chain hydrogen bonds The triple-helical trimers can often associate to form large, strong fibres Summary Describe the role of non-covalent and covalent bonds in tertiary structure Summary Understand the features of a protein from a diagrammatic representation Summary • Explain what is meant by quaternary structure • Some proteins contain several subunits formed from individual polypeptides arranged in a quaternary structure. Summary Explain the difference between globular and fibrous proteins Summary Understand the key features of keratin, fibroin and collagen