Lippincott CH2: Structure of Proteins Flashcards
How are peptide bonds formed?
Amide linkage between alpha-carboxyl group of one amino acid and alpha-amino group of another.
What is a residue?
a single amino acid in a polypeptide chain
How is a polypeptide named?
from N- to C- terminal. suffixes are changed to -yl with the exception of the C-terminal amino acid.
e.g. valylglycylleucine
Which bonds in a polypeptide can freely rotate and which can’t?
The peptide bond cannot rotate because it is shorter than a single bond and is rigid & planar.
Bonds between the alpha carbons and the alpha amino or alpha carboxyl groups can freely rotate (R group can rotate).
In what configuration is the peptide bond?
Almost always a trans bond. Due to steric interference of R groups when in cis position.
What type of enzyme cleaves peptide bonds?
peptidases (proteases)
e. g. Exopeptidases: cut at ends of proteins. Classified into aminopeptidases and carboxypeptidases.
e. g. Endopeptidases cut within a protein
How many amino acids are in each turn of an alpha-helix?
3.6 amino acids
What configuration are alpha helices in?
Right-handed spiral
Which amino acid disrupts an alpha helix?
proline, due to its secondary amino group - not geometrically compatible with right-handed spiral and causes a kink in thechain.
e. g. glutamate, asparate, histidine, lysine, and arginine also disrupt the helix by forming ionic bonds or by electrostatically repelling each other.
e. g. bulky amino acids that branch at the beta-carbon can interfere with formation of the alpha helix, in large numbers
How do hydrogen bonds in alpha helices and beta sheets differ?
amino acid residues in alpha helices space three/four resides apart participate in hydrogen bonding for stabilization of the structure
in beta sheets, all of the peptide bond components are involved in hydrogen bonding
in alpha helices, hydrogen bonds are parallel to the spiral.
in beta sheets, hydrogen bonds are perpendicular to the polypeptide backbone
what are the 2 conformations of the beta sheet?
parallel & antiparallel based on N terminal to C terminal alignment
Discuss interchain vs intrachain bonds in the beta-pleated sheet.
interchain bonds are between 2 separate polypeptides.
intrachain bonds occur when a single polypeptide folds back and bonds with itself to form the beta-pleated sheet.
to which structure are twisted beta-sheets important?
globular proteins, specifically the core of globular proteins.
***beta sheets always have a right-handed curl, or twist, when viewed along the polypeptide backbone in globular proteins
define beta-bends
Beta bends rever the direction of a polypeptide chain, helping it form a compact, globular shape. usually found on surface of protein molecules and often include charged residues.
- ** given this name because they often connect successive strands of ANTIPARALLEL beta-sheets.
- *generally composed of 4 amino acids, one of which may be proline (for kink) and glycine (smallest R group)
- beta bends are stabilized by hydrogen & ionic bonds
list the non-repetitive secondary structures
- random coil
- loop
list common motifs involving alpha helices and beta sheets
- alpha alpha (helix, loop, helix)
- beta alpha beta
- beta meander
- beta barrel
define domain.
a domain is the fundamental functional and three-dimensional structural units of polypeptides. (tertiary structure)
How many domains does a 100 amino acid chain form?
- Polypeptide chains that are greater than 200 amino acids in length generally consist of two or more domains.
* **number isn’t significant. the point of this is to know that polypeptide chains can form multiple domains
What structure drives the folding formation of tertiary structures?
interactions between amino acid side chains
list the interactions that stabilize tertiary structures of globular proteins
- disulfide bonds
- hydrophobic interaction (hydrophobic effect)
- hydrogen bonds
- ionic bonds
What amino acid forms a disulfide bond? What type of bond is this?
sulfhydryl groups (-SH) of 2 cysteine residues, covalent bond
trace formation of a protein monomer from translation in the cell
- translation results in a polypeptide (primary structure)
- formation of secondary structures (via hydrophobic effect)
- formation of domans (tertiary)
- formation of final protein monomer (folding on itself)
Why do most polypeptides, after they are denatured, not refold when returned to favorable environmental conditions.
most polypeptide folding is facilitated by a special group of proteins: chaperones (& they use ATP)
How do molecular chaperones work?
charperones facilitate correct protein folding by binding to and stabilizing exposed, aggregations-prone hydrophobic regions in nascent/denatured polypeptides, preventing premature folding
list interactions between subunits of a quarternary structure
covalent interactions e.g.
- hydrogen bonds
- ionic bonds
- hydrophobic interactions
define isoform
isoforms are proteins that perform the same function but have different primary structures
(aka isozymes, if enzyme)
define amyloid
insoluble, spontaneously aggregrating proteins, usually resulting from misfolded proteins or abnormal proteolytic cleavage of normal proteins
list amyloid diseases
- Parkinson
- Huntington
- Alzheimer
What amyloid causes Alzheimer’s?
amyloid beta (AB) ****second factor involved in the development of Alzheimer's is accumulation of neurofibrillary tangles inside neurons; abnormal form of tau protein
What kind of disease is Creutzfeldt-Jakob disease?
What causes this disease?
- Prion disease. Transissible Spongiform Encephalopathy (TSE). Found in sheep (scrapie) & cows (mad cow).
- The prion protein (PrP), called PrP^c in humans (c=cellular) is present in normal mammalian brains on surface of neurons and glial cells and serves as host protein. Infectious protein is designated PrP^sc (sc-scrapie). The infective agent is an altered version of the normal protein, which acts as a template for converting the normal protein to the pathogenic conformation - a number of alpha-helices are replaced by beta-sheets. This results in an exponential increase of the infectious form.
Why is the interchain hydrogen bond a unique characteristic to the beta-sheet and not the alpha-helix?
Interchain hydrogen bonds occur between 2 polypeptides. An alpha helix & some beta-sheets are formed by a single polypeptide - thus it has intrachain hydrogen bonding.
