FOM Week 1

the complete set of genetic info encoded in base pairs

portion of the genome that codes for a protein

control gene expression of ORF

the coding portion of a gene tat produces a functional product (eg. mRNA)

DNA regions within a gene that is not translated into protein

A DNA open reading frame has multiple introns and exons and can code for multiple RNAs via transcritpion. These RNAs can be translated into multiple proteins which can then undergo an array of post-translational modifications

1 gene--> 1 RNA--> 1 protein

study of the genome

the complete set of RNA molecules produced in a given cell or organism-unlike the genome, it can vary with external conditions

all the proteins present in a cell at any given time--more difficult to read than the transcriptome

a mutation; a change in the sequence of DNA; a single nucleotide polymorphism (SNP) can lead to genetic variation; don't necessarily know the functional consquences of all polymorphisms; can be good/indifferent or bad

Uracil on the RNA

• Adenine, thymine, cytosine, and guanine, respecitvely.
• C and G pair together, A and T (U) pair together

UAGC

N-terminus is normally on the left while the C is on the right

Arginine, Histidine, Lysine

Aspartic acid and glutamic acid

Ser, Thr, Asn, Gln

Hinders. Glycine causes a kink in the alpha helix

The three carbons of the proline side chain covalently interact with the nitrogen that forms an integral part of the backbone, forming a ring

Alanine, Isoleucine, Leucine, Methionine, Phenylalanine, Tryptophan, Tyrosine, and Valine

The squence of a chain of AAs

Alpha helices and beta sheets

The polypeptide interacts with itself so that strands forming the beta sheet are running opposite each other, such that N-termini and C-termini alternate

It occurs when certain attractions are present between alpha helices and beta sheets; it is the overall 3D structure of a single polypeptide chain

• A domain is a discrete portion of the same polypeptide that has a discrete function. It is generally larger and found in a class of proteins.
• A motif can be determined from the primary sequence and is generally smaller. It's discrete function can be found in many proteins because it is more common, broad, and less specialized than a domain

While a quaternary structure forms through controlled folding processes, an aggregation forms through an uncontrolled process of proteins sticking together and is usually pathological

The nucleus; stains it blue

• Red blood cells (orange) and collagen fibers (pink)
• It also stains the cytoplasm an intense pink when numerous mitochondria are present

The connective tissue. It stains the cartilage blu-green and the muscle fibers red

Connective tissue; it stains keratin orange, cartilage blue, bone matrix a deep blue, and muscle fibers red

Periodic acid shift: The basement membrane and carbohydrates; it stains glycogen and other carbohydrates a magenta color; Used to stain sugars

most simply, it's the protein of interest

The secondary antibody is a marker-coupled antibody that is directed against a primary antibody; it is used to amplify the signal

To maintain the integrity of the cell by regulating gene expression

The nucleus may be the same shape and color as the mitochondria, but it will always be much bigger than the mitochondria

It forms an interconnected network of tubules in vesicles within cells; its primary function is to syntehsize proteins

This is located on the RER and is the site of protein translation

sythensizes lipids and steroids, metabolizes carbohydrates and steroids, reguates calcium concentration, drug detoxification, and attachment of receptors on cell membrane proteins

Globs of protein are stored in the form of glycogen in the cell; stains very dark

Lysosomes are much darker in color than peroxisomes

They contain enzymes that break up materials within the cell and cellular debris

It processes and packages macromolecules such as proteins and lipids after their synthesis and before they make their way to their destination

They are stacked complexes

They are involved in the organization of the mitotic spindle and the completion of cytokinesis

To increased the surface area and absorption of microvilli

participates in the metabolism of fatty acids and rids the cell of toxic peroxides

It generates most of the cell's ATP supply, although it is also involved in cel signaling, cellular diffusion, cell death and the control of the cell cycle and cell growth

Enter in on the cis face and are transported out of the trans face

Mucin

8.0

below 6.9 (normal range is 7.35 to 7.45)

7.2

• 4.8 to 5.5
• These are the optimal pHs for the enzymes within the lysosome

Anywhere from 1.0 to 4.0

Histidine

Lysine and Arginine

4.0

The point at which 50% of the molecules are uncharged and 50% are charged

First, plot the pKa on the x axis. Then use intuition to decide when the compound will be positively charged and when it will be negatively charged

• Formation of a disulfide bond
• Acetylation
• Glycosylation
• Lipoylation
• Proline Hydroxylation
• Phosphorylation
• Proteolysis

The addition of an acetyl group to either the N-terminus or amino residues

The addition of a sugar residue to either a N or an O

the addition of a lipid moiety onto a cysteine residue

Proteases cut the polypeptide backbone to produce a functional protein

Ser, Tyr, or Thr

• Nothing. Alanine is small and likes to be in alpha helices
• Poly-Ala forms an alpha helix

• It is kinked. Proline is never found in an alpha helix or beta sheet. It is often found in random coils and turns.
• Poly-Pro forms a PPII helix

random coils

Preproinsulin

2. First the leader signaling sequence must be cleaved and the disulfide bonds must be formed, then the C chain must be removed

An insulin dimer. The insulin hexamer is longer-lasting

Repeating globular units (alpha and beta) of tubulin producing long twisted fibers

The "vertical" line of tubulin heterodimers. 13 of these come together to forma microtubule with a hollow center (lumen) that is approximately 10 nm thick

The hollow center of the microtubule

On the outside of the protein, facing the plasma membrane

• no predictable secondary structure
• No hydrophobic core
• A high net carge (causes the different parts of the strand to repulse each other)
• Long repetitive sequences (ie >50 Gly)
• Easily chopped up into small fragments by proteolysis
• Many of these are transcription factors
• Make up 30% of proteins in eukaryotes

• Chemistry (enzymes that catalyze reactions)
• Signaling (produce cellular responses to the environment)
• Structure (provide support and organization to cells)
• Transport (either move molecules in and out of the cells or circulate in the blood)
• Storage (allow cells to utilize oxygen, nutrients, and energy)

Changes in pH, ionic strength, pressure, temeprature, osmotic pressure, and urea (in the kidneys)

A single polypeptide that encodes on mRNA

• NMR, but only for small proteins.
• recently computer simulations have been working on it

Proteins can be grouped by common structural properties, common sequence, common function, common ligand, or common post-translational modification

Standard soluble, globular proteins; these are the ones we think of most often

• Pro-X-Gly
• (Note that proline and glycine don't like to be in normal secondary structures very often)

Integral membrane proteins

Bioinformatics

Sequence alignment

A protein with a similar general function, but with crucial differences. An example is liver pyruvate kinase and muscle pyruvate kinase

Something that binds to a protein

The protein is made of several different domains, but these domain usually have different functions

The protein has more than one function

Normal cells have microtubules that are phosphorylated and dephosphorylated in steady state equilibrium. In patients with Tau, a pathogenic Tau kinase is present that phosphorylates these filaments and drastically alters the equilibrium. The filaments aggregate to from paired helical filaments. Tau tissue contains no microtubules. This is often seen in patients with traumatic head injuries (athletes) and Alzheimer's patients

Prion proteins occur in normal conditions. Upon ingesting infected cow meat, a spontaneous mutation occurs in the the prion precursor. This mutation causes uncontrolled prion aggregation to form prion fibrils (amyloids). These elongate and then you've got problems

Pro, Ala, Taurine, Polyols (sorbitol and glycerol) and methylamines (TMAO and betaine)

Heat shock proteins and chaperonins

Folds new and misfolded proteins (small ones)

It is a protein folding machine. It folds large proteins using ATP. The unfolded protein binds to the chaperonin and using magic, the chaperonin produces a perfectly folded protein

It attaches to misfolded/old proteins, which signals a proteasome to come degrade them

Positive

• Size, with the smaller proteins moving faster and farther
• The proteins are not separated based on charge because the polyacrylamide gel swamps the charge; makes it irrelevant

Both

lining cavities, body surfaces, and tubes

Basal lamina (basement membrane works too)

To absorb, secrete, transport, excrete, protect, and sensory reception

The number of cell layers and the shape of the cells

Single layer of cells found at surfaces involved in selective diffusion, absorption, and secretion

all cells rest on the basement membrane, but the nuclei are at different levels giving it the appearance of having different layers; found in the repiratory tract and the male reproductive system

a single layer of cells characterized by folat, scale-like cells; nuclei are flat

epithelial cells that have a cube-like shape; their width is approximately equal to their height; may exist in single layes or multilayers depending on their location in the body

Epithelial cells arranged in layers upon a basement membrane where only one layer is in contact with the membrane while other layers adhere to one another; named by the most superficial layer of cells (the layer closest to the surface)

epithelia whose height are at least 4 times their width; divided into simple and stratified

lines the surfaces of hollow organs such as the kidney, urinary bladder and accessory organs: transitional cell carcinoma of the urinary system arises from this type of tissue

lining blood vessels, air sacs of the lungs; it permits the exchange of nutrients, wastes, and gases

lining the kidney tubules and glands; it secretes and reabsorbs water and small molecules

lining most digestive organs; it absorbs nutrients and produces mucus; often found near goblet cells

on the outer layer of the skin, mouth, and vaginal tract; it protects against abrasion, drying out, and infection

Lining the ducts of sweat glands; it secretes water and ions

Lining the epididymus, mammary glands, and the larynx; it secretes mucus

• Microvilli are short projections of luminal membrane containing actin filaments. They function to increase surface area of the GI tract
• Cilia are motile (ATP dependent) and much larger than microvilli
• Seterocilia are really long microvilli with a filamentous actin core and are found in the reproductive tract

• to provide structural support
• to act as a filter
• to establish polarity
• to control growth and differentation

to link epithelial cells to the basal lamina; specifically, it links the intermediate filament proteins inside the cell to the BM

Keratin

To increase surface area and thereby increase transport; they are associated with cells involved in active transport

to form a barrier at the apical surface of the epithelial cells

Connecting two epithelial cells at their most apical surface; forms a ring all the way around the cell

Links to actin cytoskeleton of 2 separate cells

Cadherins

To link intermediate filaments; these are spot welds and do not form a continuous barrier around the cell

cadherins

a direct connection between 2 cells that allows for the movement of molecules and ions between the cells

the thin layer of cells that lines the interior surface of blood vessels

Simple squamous

the cytoplasm

• The positive end
• They come off of the negative end of actin and the positive end of microtubules

to stabilize microtubules and keep them from shrinking and falling apart

GTP. When the GTP cap is removed, the GDP-tubulin dimers immediately fall apart

Microtubules use GTP wile actin uses ATP

the third group that makes up the cytoskeleton (actin and microtubules); provide much structural support

start with a protein with open N-terminus and C-terminus and lengthy alpha-helical region; 2 proteins form a coiled coil; these find another coiled coil and form a staggered tetramer (one of the coiled coils flips so that N-terminus is facing the opposite way); two tetramers pack together; 8 of these tertramers twist into a ropelike filament which is about 10 nm in diameter

one of the keratin proteins has a mutation: keratin 5/14 leads to e. bullosa (fatal); keratin 1/10 leads to e. hyperkeratosis; keratin 9 leads to e. plantopalmar

the defective keratin network cannot form strong ropes, rendering the hemidesmosomes incapable of doing their job; the layers of skin simply fall apart

6 nm; double helix

• Vimentin (mesenchyme)
• Glial fibrillary acidic protein (glia)
• Neurofilament (neurons)
• Keratins (epithelia)
• Nuclear lamins
• Desmin (muscle)

23 nm; 13 protofilaments forming a hollow tube

To tighten and hold together the actin filaments (from 74 nm to 57 nm)

The formin whiskers

It binds actin monomer and helps it bind ATP; the formin whisker then pulls the complex toward the site of the next actin addition, where profilin releases it and moves back to the original position

It puts the actin monomer in the right conformational position to bind to the actin filament, thereby increasing actin buildup

The negative ends bidn to the centrosome complex at the core and are stabilized while the positive ends radiate out and continue growing; the negative end is capped with gamma tubulin and accessry proteins in a gamma tubulin ring complex

Actin related proteins (2 and 3)

ARP 2 and 3 combine with an activating factor (unknown) and actin monomers associate with it to form the nucleated actin filament; the ARP complex then binds to another actin filament at a 70 degree angle to form an actin meshwork

Negative. It simply puts the actin in the good place to bind; does this using a wobbling motion

Uncapped filaments groaw at plus and minus ends; the capped population of filaments grows at the minus end only

• Contractile bundling (anti-parallel) is seen in stress fibers of the cells
• Gel-like networking (no real order) is seen in the cell cortex
• Tight parallel bundling is seen in the filopodium

two associated L-shaped proteins that sit on top of the actin meshwork to further stabilize it

• fimbrin (monomer); alpha-actinin (dimer); spectrin (tetramer); and filamin (dimer)
• each of these connects actin, and spaces them differently according to where they are in the body

More likely to enter the contractile bundle. The tight packing of parallel bundles prevents myosin II from entering

Crosslinks the actin filaments (seen in the microvilli)

calmodulin and myosin-I act as the lateral side arms

neurofilaments and microtubules

Heart disease, cancer, and stroke

Congenital anomalies

Unintentional injuries and congenital anomalies

unintentional injuries, cancer and homicides

unintentional injuries, suicide, and homicide

Unintentional injuries, cancer, and suicide

cancer, heart disease and unintentional injuries

Heart disease and cancer

A set of health objectives for the nation to achieve over the first decade of the new century

Initiatives pursued over the past two decades and the surgeon generals 1979 report

a well-defined region that binds ligands, can stabilize folded proteins and can change protein conformation; this region has a specific AA sequence that allows the binding to occur

a change in affinity and specificity

How tightly a ligand is bound

The dissociation constant; the point at which 50% of the protein/enzyme is bound to substrate

• Kd=[A][B]/[AB]
• given in M

M^-1

Kd=[B]

Keq=[prod.]/[react]

• The affinity is weaker
• If it shifts to the left, it's stronger

• binding one ligand makes subsequent binding more difficult;
• A protein exhibiting negative cooperativity will NEVER reach 100% saturation (bound)
• On the log curve, also a less steep slope because binding is slower

• Steeper
• Figured this out by taking the weighted average of the low affinity and high affinity sites

When a single polypeptide chain has identical binding sites, and the binding of one ligand changes the affinity of the next ligand binding

When the binding of one ligand causes the second to bind more tightly

Yes, it shifts it, depending on whether the allostery is positive or inhibitory

When a protein has binding sites for 2 different types of ligands, and the binding of one ligand changes the affinity for the other

It shifts to the right because the affinity for the second ligand becomes weaker

Neither ligand wants to bind as much when the other ligand is already bound

It shifts to the left because the affinity is strengthened by the binding of the first ligand

REGULATION! it allows the cell to adapt to changing conditions

Changing nutrients allows the reaction rates to be turned up or down

Can change transcriptome/proteome in response to the environment

Allostery involves 2 different ligands (one is usually an effector) at 2 different binding sites; cooperativity involves identical binding sites and the same ligands

No, it merely changes the slope

the rate of NEW cases of disease in a susceptible population in a given period of time

incidence=(# New cases of disease)/(# at risk in population in a given time period)

ALL cases of disease (new and old) in a susceptible population; depends on incidence and duration of disease

prevalence= (# new and old cases of disease)/(#people in pop. at that point in time)

(total # deaths in a period)/(# of people in pop. mid-period)

How spread out things (data points) are in a population

How spread out is the sample mean

Null hypothesis--assume that the opposite of what you wish to prove is true; the hypothesis of no difference

A measure of how likely it is that what we have observed could occur randomnly; use a p-value of 0.05

t-test

Chi-square test

statistical test used to compare the mean values between 2 different groups

statistical test used to compare proportions between 2 different groups

A range of plausible values for the difference; if a 95% confidence interval for a difference does not contain 0, then the p-value is less than 0.05

it is less the 0.05

• ~18% identical and ~38% similarity
• Secondary and tertiary structures are very similar; they bind the same prosthetic group (heme) and the same ligand

• Mb is a monomer
• Hb is a tetramer with 2 alpha subunits and 2 other subunits (usually beta, but doesn't have to be)

Mb does, needs to steal it from Hb to take to muscles

There is a reduction in the amount of oxygenated blood leaving the lungs; more of it is reduced

There is an increase in the gaseous pressure of oxygen in the reduced blood returning from the tissues; becoming acidotic

There is a decrease in the percent saturation of the oxygenated blood leaving the lungs

A disorder characterized by the presence of higher than normal level of methemoglobin (metHb) in the blood. This metHb has an extremely high affinity to oxygen, resulting in almost no oxygen delivery to the tissues