Lecture 7 Flashcards
Primary protein structure:
represented as a simple line and is simply the order amino acids are linked together (amino acid sequence)
Secondary protein structure:
the polypeptide backbone exists in different section of a protein either as an alpha helix, beta sheet, or random coil
Tertiary protein structure:
the secondary structures are folded into the compact globular protein, 3D structures
Quaternary protein structure:
protein molecules known as subunits assemble into a multimeric protein held together by weak forces (multiple subunits)
Properties of the primary structure:
- proteins are long
- proteins are similar but not identical
- changes are tolerated depending on where they occur within the 3-D structure of the protein
Conservative protein changes:
preserve chemical properties or size of the side chain
Nonconservative protein changes:
changes that result completely different side chains type or size
What determines primary protein structure:
the genetic code
Codon:
nucleotide triplets are used to code for each amino acid
Number of amino acid combinations vs. number of amino acids:
64 possible combinations code for 20 amino acids
Linus Pauling’s rules for secondary structure:
- bond lengths and nalges of amino acids and peptides must stay fairly consistent to those observed by diffraction studies
- no atoms should approach more closely than their Van de Waals radii. steric restrictions make up the peptide backbone
- six atoms in the peptide-amide should be coplanar. Rotation is possible around bonds and adjacent to alpha carbon. remain in trans configuration
- noncovalent bonding is necessary to stabilize structure, usually hydrogen bonding between amide protons and carbonyl oxygen
Rotations about single bonds in a polypeptide:
peptide bonds cannot rotate, but their adjacent carbon/nitrogens can: allows unique folding of proteins into many different 3D structures
Phi bond:
bond between N amide and alpha C
Psi bond:
bond between the alpha C and carbonyl C
Most frequent forms of secondary structures:
alpha-helix and beta-sheet, in each structure the amide group is planar and all amide protons and carbonyl carbons are involved in H-bondings
Properties of alpha helix:
- rod-like in structure
- inner backbone with R group extending outward
- C-O and N-H, H-bonding hold 2o structures in place
- Right-handed most
- Side chains project outwards
H-bonding pattern of alpha helix:
C=O — H-N via
Structure features of alpha helix:
- Right handed helix: 3.6 residues
- H-bond between every 4th aa between the oxygen of the carboxyl group and the hydrogen of the amino group (before and after)
- R groups project out from helix, generally towards the N terminal end of the helix
- H-bonds (orange) are parallel to axis of the helix
- the sturcture can be in hydrophobic or hydrophilic environments
Properties of beta strands and beta sheets:
- strand + strand = sheet (from same polypeptide)
- fully extended. often in hydrophobic core of a protein
- distance between adjacent a.a. is 3.5 A
- parallel and anti-parallel sheets are possible
What leads to parallel and anti-parallel configurations:
- unique H-bonding properties
- antiparallel arrangement can arise by “hairpin folding” of a single strand
Properties of polypeptide (polyproline) II helix:
- does not satisfy H-bond requirements
- left-handed
- these structures tend to have many prolines that kink
- glycine are often found as well because they are smaller
Positions of alpha-helix and beta sheets:
can have amphipathic characteristics so one face is hydrophobic and one is hydrophilic (i.e. an alpha helix will have side chains of similar polarity every 3-4 residues, whereas a standard B-strand will have alternative polar and nonpolar side-chains)
Side chains on alpha helix:
radiate away from the helical axis
Side chains on beta sheet:
located on opposite faces of the sheet
Determination of peptide bond conformations:
some combination of phi and psi angles are now allowed due to steric intereactions. in the alpha-helix (b), the backbone atoms are already closely packed and R groups project out
Ramachandran Plots:
- white regions correspond totheoretically allowable conformations
- grey dots represent the areas of angles
- each amino acid has its own Ramachandram Plot
Avaliable secondary structure based on Ramachandran plots:
- beta strand
- alpha helix
- 310 helix
- polypeptide II helix
Types of proteins:
fibrous (long and extended) and globular (blobs)
Fibrous proteins:
each tends to be enriched with 3-4 particular amino acids, which stabilize their particular structure
Amino acid composition of collagen:
glycine, alanine, and proline
Amino acid composition of most proteins:
glycine, alanine, and leucine
Properties of collagen:
- each polypeptide is a left-handed helical structure with glycine, and proline
- Gly-Proline or Hydroxy-Proline repeats
- Tropocollagen: 3-left handed helices favored by Proline joine to form a right-handed tripple helix
- Cross-links between lysine residues form between helices to form a collagen fibril
What links collagen:
hydrogen bonding between amide protons and carbonyl carbons, but hydroxyproline also links the triple helices
Secondary and tertiary structure of collagen:
the same as each other
Primary structure found in collagen:
quatenary structure
Function of hydroxyproline:
makes collagen tougher by cross-linking strands by acting as a hydrogen donor and acceptor
How are hydroxyproline composed:
an addition to proline after translation
Vitamin C and hydroxyproline:
enzymes that catalyze hydroxyprolation of proline require Vitamin C to function. less vitamin C reduces hydroxyproline that keeps collagen together, weakening
Symptoms of Scurvy:
- anemia (small-cell type)
- atherosclerotic plaques
- pinpoint hemorrahages under the skin, bone fragility, joint pain
- poor wound healing, frequent infections, bleeding gums, loosened teeth
- muscle degeneration and pain, hysteria, depression, rough skin, blotchy brusies
How are tertiary structures stabilized:
by noncovalent bonds and sometimes covalent disulfide bonds between Cysteines
Tertiary structures of globular proteins:
- myoglobin with heme group pocket. 8 alpha-helices form a pocket
- alpha/beta barrel encloses hydrophobic side chains
- pyruvate kinase with 3 domains: cap covering catalytic site, catalytic domain, and regulatory domain
Protein domains:
- compact globular units that are connected by flexible regions
- make up regions of a protein
- can be large
- stable; can be associated with specific function(s) of protein
Supersecondary structures:
repeated secondary structure motifs within a tertiary structure (domain)
Abrupt chages in polypeptide chain direction:
hairpin turns stabilized by H-bonds
Free Energy of folding of a protein:
spontaneous reaction driven by a low Delta H because bonds formed between folded proteins replaced those formed between surroundings
Entropy of protein folding:
folding is more ordered; however, in an unfolded state the water molecules are more ordered around the structure, thus it is usually more favorable to fold the molecule
Stability of protein folding:
highly unstable, can be unfolded with slight increases in temperature
