chapter 8- protein folding and structure

primary amino acid structure characteristics

the amino acid sequence

starts with the amine group of the first amino acid (N terminus)

ends with the carboxyl group of the last amino acid (C terminus)

relatively easy to predict the primary amino acid structure- based on codons that are encoded in the DNA and transcribed into mRNA to be translated at the ribosome

secondary amino acid structure characteristics

an amino acid chain that can fold

two basic secondary amino acid structures: alpha helix and beta sheet

both structures result from hydrogen bonding between amine and carboxyl groups of distal amino acids

proline disrupts some secondary structures and is often at the end of a helix, bend, turn or loop, rather than within these structures

alpha helix formation

alpha helix secondary amino acid structure is formed when a linear chain of amino acids forms into a spiral

amino acids that are internal to the peptide chain hydrogen bond to other amion acids that are four amino acids far away

beta sheet formation

when a linear chain of amino acids forms into an aligned sheet

amino acids that are internal to the peptide chain hydrogen bond to other amino acids that are part of another part of the peptide chain

in a parallel beta sheet, both parts of the chain run in the same orientation
the parts of the beta sheet can be antiparallel, with the two parts of the peptide chain running amine group to carboxyl group and the other carboxyl group to amine group

tertiary amino acid structures characteristics

when secondary structures come together with the help of several different forces

H bonding can bring a peptide chain together into secondary structures and can also contribute to tertiary structures

side chains of the amino acids involved can cause ionic and hydrophobic interactions

presence of cysteines in the protein- potential for disulfide bonds to form within the structure

quaternary amino acid structure characteristics

two or more tertiary structures come together

same forces that contribute to tertiary structures are involved

proteins come together as dimers, trimers, or more

can be two copies of the same protein or different proteins

subunits- individual proteins

the role of chaperones in folding proteins

DsbA and DsbB aid in the formation of disulfide bonds

DsbC and DsbD will remove the incorrect disulfide bonds

constant redox reaction- breaking and forming of disulfide bonds

describe the functions of DsbA and DsbB

DsbA is responsible for the formation of disulfide bonds and reduces itself

DsbB- recycles DsbA and brings it back to its oxidized self

describe the functions of DsbC and DsbD

DsbC- breaks the disulfide bond when its misfolded

DscbD- recycles DsbC after it breaks the the misfolded disulfide bonds

phosphorylation

modification: addition of a phosphate group

kinases phosphorylate proteins
phosphatases dephosphorylates proteins

effect: often activating the protein

most common: tyrosine, arginine, and serine

lipidation

modification: addition of a lipid

occurs within the cytoplasmic membrane
a lipobox is an amino acid sequence that signals lipidation

effect: enables the protein to be anchored to the membrane via the hydrophobic nature of the lipid

glycosylation

modification: addition of a glycan (polysaccharide): O-linked or N-linked

N-linked occurs at the amine of asparagine
O-linked glycosylation adds a sugar to the hydroxyl groups of serine and threonine

occurs on the outer surface of the bacteria after the protein passes through the membrane

effect: common modification of adhesins and flagellar proteins

hydroxylation

modification: addition of a hydroxyl group

added to lysine and proline residues

effect: helps maintain accuracy during translation - elongation and termination factors and ribosomal proteins

acetylation

modification: acetyl group

added to the N-terminus of the protein: irreversible and neutralizes the zwitterionic positive charge of the amine end of the peptide chain

also added to the R group of lysine residues: reversible

addition mediated by acetyltransferases

succinylation

modification: addition of a succinyl group

added to the R group of lysine residues: in competition with acetylation

methylation

modification: addition of a methyl group

added to the R group of lysine residues: in competition with acetylation and succinylation

effect: various including virulence

nitrosylation

modification: addition of a thiol group

added to the R group of cysteine residues

S-nitrosylated cysteines cannot participate in disulfide bonds- impact secondary structure of protein

effect: regulates protein activity and function

modification of N-formyl methionine

modification: removal of formyl group or fMet

removal of formyl group is performed by deformylase

removal of fMet is performed by methionine aminopeptidase- only when the adjacent amino acid is small