General Information Flashcards
Four organizational levels of protein structure:
- primary
- secondary
- tertiary
- quaternary
Primary structure
- sequence of amino acids in a protein
- defined by covalent bonds (including disulfide bridges)
Peptide bonds covalently link amino acids via:
- amide linkages between the α-carboxyl group of one amino acid and the α-amino group of another amino acid.
- occurs via a loss of water
All amino acid sequences are read from…
- the N- to the C-terminus of the peptide
Peptide bond characteristics (4):
- partial double-bond character
- rigid and planar
- uncharged, but polar
- trans configurations (except proline, cis 15%)
The -C=O and -NH groups of peptide bonds are …
- polar and involved in hydrogen bonds in alpha helices and beta sheet structures
What angles specify the path of a polypeptide backbone?
- phi and psi angles
- only two sets of phi and psi angles can be repeted without steric collisions
_____ is the only amino that can cause a cis configuration in a polypeptide chain.
Proline
15% of the time
Peptide bonds have trans configurations to minimize:
steric hindrance. Orients side chains on opposite sides of the peptide bonds. Proline can cause cis configuration.
Repetitive phi and psi bonds in polypeptide chains aid in the formation of:
repetitive secondary structures
- alpha helices (coiled chains)
- beta sheets (extended chains)
Non-regular and non-repetitive secondary conformations are due to:
non-repeating phi and psi angles
- coils
- turns
- loops, etc.
Secondary Structure
Local arrangements of the peptide backbone, often defined by H-bonds
Tertiary Structure
Arrangement of secondary structure elements into compact domain
Quaternary Structure
Arrangement of multiple polypeptide chains in a multi- subunit protein (only in proteins with >1 chain)
Alpha helix dimensions:
- 3.6 residues / turn
- 5.4 Å / turn
- 1.5 Å rise / residue
Hydrogen bonding in alpha helices:
Residue i forms a hydrogen bond with i + 4.
- Not all hydrogen bonds are satisfied, but within the body of the helix, every NH group forms a hydrogen bond with a carbonyl oxygen. This neutralizes the polarity of the peptide bond, and stabilizes the entire structure.
In an alpha helix, side chains extend…
outward from the helix to avoid interacting sterically with each other
In an alpha helix, all carbonyls extend toward…
the C-terminus
creates polarity to helix
Interiors of proteins are largely …
repetitive secondary structures
Amino acids that can disrupt an alpha helix:
- proline (secondary amino group not compatible with right-handed spiral of helix; kinks)
- large numbers of charged amino acids (form ionic bonds or repel each other)
- amino acids with bulky side chains (Y)
- amino acids that branch at beta-carbon (V and I)
Alpha helix characteristics:
- right-handed
- C=O point to C-terminus (dipole)
- H-bonds (between C=O and H-N; residue i and residue i+4)
- 3.6 residues / turn
- 5.4 Å / turn
- 1.5 Å rise / residue
Hydrophobic helices:
- hydrophobic (nonpolar) sidechains
- typically go through lipid bilayer
Polar helices:
- typically charged side chains
- exposed to solvents (intracellular and extracellular)
Amphipathic helices:
- a mixed pattern of polar residues, hydrophobic residues, and charged residues.
- Can have polar faces and non-polar faces.
In alpha helices, hydrogen bonding is:
- between the peptide-bond carbonyl oxygens and amide hydrogens that are part of the polypeptide backbone (i and i + 4 residues H-bond)
- parallel
Unlike alpha helix, beta sheets are:
- composed of two or more polypeptide chains
- almost fully extended
- H-bonds are perpendicular to the polypeptide backbone
The three perpendicular planes of beta sheets:
- plane of strands
- plane of hydrogen bonds
- plane of side chains
Dimension of Beta-sheet:
- about 3.5 Å / residue
Two types of Beta Sheets:
- Parallel
- Antiparallel
Parallel Beta Sheets
- hydrophobic (N-N-N-N-N-N-N)
- buried in protein interior
- N-termini line up with one another, C-termini line up with one another
(N=nonpolar)
Antiparallel Beta Sheets
- amphipathic (N-P-N-P-N-P)
- N-terminal and C-terminal ends alternate
- one face hydrophobic, one face polar.
- Polar face is on surface, and hydrophobic face buried on interior.
Beta sheet hydrogen bond and side chains:
- side chains perpendicular to sheet (above and below)
- hydrogen bonds parallel to sheet
Turns and loops are:
secondary structures, just not as regular/repetitive as helices and sheets.
Turns and loops largely make up:
- the surface of proteins
Turns and loop are often the sites of:
- functional residues/binding sites (since turns and loops compose the surface of globular proteins)
- Alpha helices and beta sheets provide scaffold for these loops and turns
Approximately ___% of an average globular protein is organized into repetitive structures such as the alpha helix and/or beta sheet.
50%
The remainder is made up of nonrepetitive loops, turns, and coils.
Helix-loop-Helix Motif
loop can be large or small
Beta-hairpin Motif
antiparallel sheets
Greek Key Motif
- a fold of a large antiparallel beta hairpin.
- Fold over a long beta strand.
- Create really common and stable structures. This fold is in immunoglobulins.
Beta-Alpha-Beta Motif
- connect two parallel beta strands in a beta sheet.
- Loop through amphipathic helix.
Five forces that stabilize protein structure:
- Hydrophobic Interactions
- van der Waals Interactions (very small, due to tight packing of residues)
- Hydrogen Bonds (inter- or intrachain or with water)
- Ionic Interactions (between positively and negatively charged side chains)
- Disulfide Bridges (covalent bond between cysteines)
Domains are:
- the fundamental functional and 3-D structural units of polypeptides
- 100-300 amino acids
Domain cores are built from:
- combinations of super-secondary structural elements (motifs)
- Folding of a domain occurs independently of the folding of other domains in a protein
Typical weight of a single domain:
- 10-30 kDA
Folds of proteins consisting of all alpha proteins:
- mostly alpha helices
- all perpendicular orientations or all parallel orientations.
Folds of proteins consisting of all beta proteins:
- usually have little bits and pieces of helices
- core of protein made of anti-parallel beta strands
Folds of proteins consisting of both alpha and beta proteins:
- parallel beta sheet usually connected by alpha helices.
- Can wrap around in barrel or go around in a flat sheet.
Subunits of quaternary structures are held together via:
- non-covalent interactions
- H-bonds
- ionic bonds
- hydrophobic interactions, etc.
- subunits may function independently or cooperatively (i.e. hemoglobin)
Isoforms:
- proteins that perform the same function but have different primary structures
- If the isoform protein is an enzyme, then it is referred to as an isozyme
Native conformation:
- the functional, fully-folded protein structure
- determined by primary structure (AA sequence)
- AA interactions guide secondary, tertiary, and sometimes quaternary structure
Protein chaperones assist with:
the proper folding of many species of proteins
