BIOL 111 Lecture 7 Protein Structure and Function I (2018) PDF

Primary Structure • The primary structure of a protein is the sequence of amino acids, N-terminal to C-terminal • This can be written out as a linear sequence using standard abbreviations for amino acids e.g. Met-Ala-Ala-Glu-Cys-His-Gly etc • Alternatively, single letter code can be used e.g. MAAEC...

Primary Structure • The primary structure of a protein is the sequence of amino acids, N-terminal to C-terminal • This can be written out as a linear sequence using standard abbreviations for amino acids e.g. Met-Ala-Ala-Glu-Cys-His-Gly etc • Alternatively, single letter code can be used e.g. MAAECHG Translate the following into single letter code: Ile-Ala-Met-Ala-Pro-Glu-Pro-Thr-Ile-Asp-Glu Secondary Structure • The secondary structure of a protein is the folding of parts of the primary sequence into particular structures • These usually involve several amino acids that may be contiguous or from different parts of the primary structure • There are two important types of secondary structure – the alpha (Greek letter α) helix and the beta (Greek letter β) sheet PROTEIN FOLDING The main driving force in protein folding is to attain an energetically stable structure. For water soluble proteins it is essential to pack hydrophobic side chains into the interior of the protein to ‘hide’ them from the surrounding water molecules. This forms a hydrophobic core (similar process to oil forming droplets in water). As the main polypeptide chain is hydrophilic because of the polar C=O and N-H groups, the protein must adopt structures which ‘neutralise’ these groups by hydrogen bonding. The α helix I α helices are usually formed from stretches of 5-40 amino acids The main chain N-H and C=O groups are hydrogen bonded to one another along the axis of the helix The a helix is very stable The α helix II There are 3.6 amino acids per turn. Each amino acid turns the helix through 100° The vertical distance from one amino acid to the next is 0.15nm so the pitch of the helix (turn length) is 0.54nm The C=O group of amino acid n is hydrogen bonded to the N-H group of amino acid n+4 The α helix III The amino acid side chains project out from the edge of the helix The α helix IV The sequence of amino acids in an a helix can be plotted on a helical wheel diagram. Each residue is plotted 100° around a circle or spiral The β sheet β sheets are formed from non-continuous regions of the polypeptide chain. These regions are called b strands The b strands line up and form hydrogen bonds between the C=O groups of one strand and the N-H groups of another If the strands all run in the same direction (remember that proteins have a direction, N → C) then the b sheet is described as PARALLEL. If the strands run in opposite directions then it is said to be ANTI-PARALLEL The parallel β sheet The anti-parallel β sheet Pleated structure of the β sheet b sheets, (parallel and anti-parallel), are often called b - pleated sheets because the Ca carbons lie successively above and below the plane of the sheet Loop regions I Secondary structures (a helices, b sheets) are linked by loop regions Loops vary in length. Long loops are called random coils and are highly flexible parts of proteins. Short loop regions which connect anti-parallel b strands are called hairpin loops or b turns Loop regions II PROLINE is often found in loop regions because its locked ring structure introduces a ‘kink’ into the polypeptide chain. GLYCINE is also often found in loops because its small side chain enables it to form turns when other amino acids could not. β-α-β motif Although anti-parallel b strands are usually connected by hairpin loops, parallel b strands are usually connected by an a helix The helix crosses the b sheet from one edge to another This is called a b-a-b motif Post-translational modifications • • • • • • Proteins are always synthesised using the same set of 20 amino acids However, they can be modified after synthesis (translation) in various ways Alterations to some produce the “rare” amino acids – hydroxyproline, hydroxylysine Sugars/carbohydrates/glycans can be added to some amino acids (asparagine, threonine, serine) this is called glycosylation – glycoproteins (N-linked, O-linked) Lipids can also be added – lipoproteins These various post-translational modifications can contribute to secondary structure 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 PRIMARY STRUCTURE Formation of a helices and b sheets SECONDARY STRUCTURE Correctly folded compact domains TERTIARY STRUCTURE Kahoot! Summary • Describe the features of the alpha helix • N-H and C=O groups are hydrogen bonded to one another, 3.6 amino acids per turn, C=O group of amino acid n is hydrogen bonded to the N-H group of amino acid n+4……………………………. etc…. • Describe the features of the beta sheet • non-continuous regions of the polypeptide chain, b strands line up and form hydrogen bonds between the C=O groups of one strand and the N-H groups of another, If the strands all run in the same direction (remember that proteins have a direction, N → C) then the b sheet is described as PARALLEL. If the strands run in opposite directions then it is said to be ANTI-PARALLEL………………………. etc Summary • Explain the role of loop regions in joining together elements of secondary structure Summary • Appreciate the range of post-translational modifications to proteins • These various post-translational modifications can contribute to secondary structure