3 - Protein Structure

do changes in the DNA result in change in the RNA

some

not all DNA mutations are in region of the genome that is transcribed

types of RNA

mRNA - encodes proteins

tRNA - acts as adaptor between mRNA and amino acidds

rRNA - forms the ribosome

snRNA - functions in various nuclear processes

snoRNA - facilitates chemical modifications of RNAs

miRNA - regulates gene expression

siRNA - silences gene expression

lncRNA - regulates gene expression

snRNAs (small nuclear RNAS) spotlight on health

heavily involved in formatio of spliceosome with mutations leading to spliceosomopathies

aggregates of snRNA sometimes found in brain of alzheimer’s disease patients

snoRNAs (small nucleolar RNAs) spotlight on health

involved in maturation of other types of RNAs and ribosome function

biomarkers for cancers

miRNAs (microRNAs) spot light on health

regulate gene expression

mutations in miRNAs are involved in many human diseases including cancer and neurodegenerative disorders

siRNAs (small interfering RNAs) spotlight in health

play role in RNA interference

in vitro manipulation of gene expression

lncRNAs (long noncoding RNAs) spotlight in health

major regulators of gene expression

Xist is lncRNA responsible for X inactivation in XX females to facilitate dosage compensation

synonymous changes

changes in the coding region that do not result in amino acid changes

nonsynonymous changes

changes in the coding region that result in amino acids changes. replacement changes

categories of silent mutations

1. synonymous changes

2. any mutation in non-mRNA RNA

3. any mutation in a DNA that is not transcribed

why does protein structure matter

protein structure determines properties and therefore function

what does secondary structure determine

how the amino acids interact with one another

internal bonds are rotatable

terminal bonds do not rotate

how many conformations does a protein possibly have

count the rotatable bonds

each amino acids has two bonds

each bond has three possible conformations

hydrophobic effect

tendency of nonpolar molecules to form aggregates in water

hydrophobic effect is major dirver of what

major driver of folding

what other forces play a role in protein folding

1. hydrophobic effect

2. molecular interactions (van der Waals)

3. thermodynamics

what do you need to form hydrogen bond side chains

1. need H bonded to an elec neg atom (donor)

   1. or a electronegative atom (acceptor)

secondary structures

• alpha helices

• beta sheets

are anti parallel or parallel sheets stronger

antiparallel

they have linear hydrogen bonds

secondary structure loops

connecting alpha helices and beta sheets

• relatively dynamic and floppy

• form irregular structures and hydrogen bonds

secondary structure beta turns

tight turns

MALEK amino acids readily form alpha helices

Methionine

Alanine

Leucine

E Glutamic Acid

K Lysine

which two amino acids DONT work well in alpha helices

glycine - too loose

proline - too rigid

what do cysteins form

form disulfide bonds that stabilize protein structure

last molecular interaction

protein folding funnel

proteins fold by a biased search - nonlinear

proteins at the bottom tip settle into the 3D fol, the native state

at the very bottom there is the least amount of energy