Dunn M&C - A bunch of terms for the final.

kinase

transfers a phosphate from ATP to something else.

• use of phosphatases

phosphorylation

a reversible post-translational modification that regulates protein function

• causes conformational change in proteins that either activate (top) or inactivate (bottom) the protein’s function

phosphatase

an enzyme that removes phosphate groups from molecules.

cyclin-Cdk complex

regulates the cell cycles and drives each phase of the cycle

• cyclin concentrations changes, whereas the Cdk component is present at constant levels

• when their job is done, cyclin is degraded (so cell cycle can only move in the forward direction)

• contains heterodimers of cyclin and cDK

heterodimers

a complex formed by the association of two different protein subunits

• e.g, cyclin-Cdk is one, cyclin and Cdk

Cdk

a kinase itself

intercellular signals

communication between cells

• usually small soluble molecules that may be protein/nonprotein

intracellular signals

communication inside cells

• usually small soluble molecules that may be protein/nonprotein

autocrine signaling

same cells emits and receives signal

paracrine signaling

signal diffuses only microns away

• many signals are peptide “growth factors”

juxtacrine signaling

a.k.a contact-dependent signaling, the cells must be immediate neighbors because the signaling molecule is attached to the signaling cell

endocrine signaling

signals that diffuse over long distances

• e.g, circulatory system through blood stream

receptors

signals are received by cells through these protein complexes

• not all cells respond to all signals

• a cell must express the receptor for that signal

intracellular receptors

receptors residing inside the cell

• small, nonpolar signaling molecule passes through the PM and activate cytoplasmic receptors

cell-surface receptor

receptor embedded in the plasma membrane

• polar signaling molecules cannot pass the PM and rely on cell-surface receptor$

lipid-soluble signals

diffuse directly across the membrane and bind to intracellular receptors

• signal directly by inducing a conformational change in an intracellular receptor, bringing a change in cell behavior

lipid insoluble signals

binds to cell surface receptors that link the external environment to the cell interior

• hydrophilic

• wont pass through PM

signal

change in gene expression or other cell behavior

signal-transducing receptors

on the surface of cells, these are what intercellular signals usually bind to

• signal binds to receptor which is activated by a conformational chage

signal transduction

the conversion of the extracellular signal to an intracellular signal

kinase receptors

a second large class of receptors that are used for cell communication

• receptor tyrosine kinase: epidermal growth factor

receptor tyrosine kinases (RTKs)

cell surface receptors that undergo ligand-induced dimerization

• control a more limited set of cell behaviors — they usually promote cell proliferation, survival, and tissue growth

• activated by ligand-induced dimerization

ligand

extracellular signal

cross-phosphorylation

process where one protein kinase phosphorylates another protein kinase, eachother

• two tyrosine domains

• normal rtk activation

dimerization

process where two similar or identical molecules (monomers) combine to form a larger unit called a dimer

• e.g, kinase domains in RTK activation

ligand-induced dimerization

process where a ligand triggers the formation of a dimer (two identical or similar molecules joined together) by binding to a receptor protein

kinase domain

a portion of the protein that can remove a phosphate from ATP and transfer it to something else

trans-phosphorylation

each member of the receptor pair attaches phosphate groups to the other member

recruitment and activation of cytoplasmic signaling proteins

the attached phosphate groups provide binding sites for intracellular signaling proteins

tyrosine side chains

Have a hydroxyl group to which phosphate can be covalently attached;

These phosphotyrosines create new binding sites for cytoplasmic signaling proteins, recruiting them to the membrane

Ras protein

family of small GTPases that play a crucial role in activating the MAP kinase signaling pathway.

• RTKs generate intracellular response through Ras

GTPase

family of enzymes that regulate various cellular processes by hydrolyzing guanosine triphosphate (GTP) to guanosine diphosphate (GDP

Ras GTPase

formation of this signaling complexes Ras to exchange its GDP for GTP, rendering it active

kinase cascade

leads to the phosphorylation of target proteins which brings about a change in cell behavior. each kinase phosphorylates and activates the next

• activated by activated RAS

Ras-GTP

activates the kinase/phosphorylation cascade

• active

Ras-GDP

inactive

GTP exchange

binding of cytoplasmic signaling proteins leads to stimulation. this exchange leads to a conformational change in the G-protein, activating it and initiating downstream signaling cascade

• occurs when a G protein (=GTPase) releases its bound GDP and binds instead to a GTP

G protein-coupled receptors (GPCRs)

huge class of signaling receptors that share a common structure and mechanism of signal transduction

• G protein binds to the cytosolic tail or loop

• induces g protein to replace GDP with GTP (GTP exchange)

• active version often change level of second messenger

G proteins

activated when a ligand binds to a G protein-coupled receptor (GPCR), triggering a conformational change in the receptor that in turn causes the G protein to release GDP and bind GTP

• associated with membrane by lipid anchors

• peripheral membrane proteins

cytoplasmic signaling proteins

adaptor protein and ras activating proteins

second messenger

small intracellular signaling molecules that transmit signals from the cell surface to the inside of the cell, mediating the effects of first messengers

• temporarily increases or decreases in response to an extracellular signal.

• its small, diffuses rapidly and helps to relay the signal to other signaling proteins inside the cell

adenylyl cyclase

catalyzes conversion of ATP into second messenger cyclic AMP (cAMP)

GPCR amplification

occurs when one molecule in a relay leads to multiple active molecules

signal amplification

allows a cell to be (sometimes exquisitely) sensitive to incredibly small concentrations of signaling molecules

• occurs when one ligand induces many copies of an intracellular signal. this can be accomplished by the activation of an enzyme

signal transduction

the conversion of the extracellular signal to an intracellular signal

signal termination

1. signal goes away

2. G protein hydrolyzes GTP to GDP

3. phosphatases remove phosphates from activated targer proteins (pink)

4. Phosphodiesterases cut the cyclic bond in cyclic AMP (to yield just AMP, which is inactive)

binding affinity

The amount of time a signaling molecule remains bound to its receptor depends on how tightly the receptor holds on to it

GPCR functions

changing the intracellular concentration of a second messenger or by altering the activity of the ion channels, which changes the membrane potential

membrane potential

charge differential across plasma membrane

Cellular Response w/ speed & quality

Responses to a signal may vary according to the cell type because each cell only expresses a subset of receptors

• e.g, Alter metabolism, Alter gene expression, Survive/die, Move/change shape, “Fire”, Proliferate (enter S phase), Alter ion permeability, Secrete something, Fuse with another cell

signal integration

information processing in the brain: multiple variables determine the outcome

• cells usually integrate the signals they receive

• combinatorial control and contributes to regulation of gene

  expression

phosphodiesterases

cuts cyclic bond in cyclic AMP (cAMP) to yield just AMP, which stops the phosphorylation and activation of target proteins

protein functions

1. structural support

2. membrane channels (control the movement of ions and molecules across cell membranes)

3. act as enzymes

4. signaling (function as receptors, hormones, or intracellular messengers to regulate cellular activities)

amino functional group

-NH2 — typically acts as a base, so it can collect a proton (H+). And when it collects a proton, it gains a full + sign.

carboxyl functional group

-COOH — typically acts as an acid, so it can donate a proton. And when it donates a proton, it gains a full - sign.

hydroxyl functional group

-OH; highly polar, so makes compounds more soluble through H-bonding with water; doesn’t dissociate or ionize in physiological conditions

phosphate functional group

several phosphate groups linked together, breaking these O-P bonds between them releases large amounts of energy

sulfhydryl functional group

when present in proteins, can form disulfide (S-S) bonds that contribute to protein structure

amino acid structure

N-C-C: amino group, a carbon (connected to H and R-Group/side chain), and carboxyl group. tetrahedral arrangement

side chains

also known as R-group, are the most important to the functional aspects of protein; gives amino acids its unique character

central carbon

also known as the alpha (α) carbon, is present in amino acids.

non-ionized form of amino acids

represented in solid state/neutral structure

ionized form of amino acids

represented in cells/aqueous state: N will often accept a proton as a fourth covalent bond, and carboxyl group are always willing to give up a proton at a physiological pH

zwitterion

a molecule that has both a positive charge and a negative charge, but an overall neutral charge

amino acids types

there are 20 common amino acids; they are grouped based on how well they interact with water (philic or phobic), or whether they are basic or acid or polar uncharged.

Alanine

common amino acid; has a methyl group

Methionine

common amino acid; not too polar

Phenylalanine

common amino acid; bulky and hydrophobic with a carbon ring

glycine (gly, G)

a special amino acid; gives the amino acid more flexibility especially in the polypeptide backbone, the side chain is just a hydrogen group (H)

proline (pro, P)

a special amino acid; present in polypeptides and it can constrain how a polypeptide chain forms due to the restriction of rotation of the C-N backbone

cysteine (cys, C)

a special amino acid; the only amino acid with a sulfhydryl group, two of these can form disulfide bonds, forming cross bridges that connect different parts of the same protein or different proteins

amino acid w/ hydrophilic side chains

amino acids with polar side chains have a perm. partial charge. they are hydrophilic and tend to form hydrogen bonds w/ one another or water molecules. basic & acidic amino acids are strongly polar and hydrophilic. these basic (+) and acids (-) are charged and these charged groups can form ionic bonds with one another and other charged molecules.

process of creating peptide bonds between amino acids

the carboxyl group of one amino acid reacts with the amino group of another amino acid, and dehydration synthesis/condensation occurs (release of a water molecule). this is catalyzed in the large subunit of the ribosome. ** Practice drawing these

condensation reactions

build polymers from monomers; peptide bond formation

hydrolysis reactions

break polymers back into monomers; peptide bond cleavage

peptide bond cleavage

the process of breaking the covalent bonds that connect amino acids in a protein; catalyzed by proteases that require no energy

protease

a hydrolase enzyme; breaks polypeptides

primary structure of a protein

sequence of amino acids which determines the shape into which it will fold, which in turn determines how it will function

secondary structure of a protein

alpha helices and beta sheets, which result from hydrogen bonding interactions between backbone atoms; at least one (alpha/beta) is present in virtually all proteins. H-bonding is the backbone for secondary structures

tertiary structure of a protein

the three-dimensional shape, usually made of several secondary structure elements. this structure determines the proteins function.

quatenary structure

the interaction between more than one polypeptide chain; two or more tertiary structures come together to form the functional protein. these are held together by van der Waals forces, hydrogen bonds, disulfide bonds and ionic bonds. these still have N and C-termini for each polypeptide

amino (N-) terminus

corresponds to a protein’s first amino acid; proteins are always synthesized from amino- to carboxyl terminus

carboxyl (C-) terminus

corresponds to a protein’s last amino acid; proteins are always synthesized from amino- to carboxyl terminus

pentapeptides

several amino acids; have a backbone which will determine secondary structures (remains the same regardless of which amino acids are present_

alpha helices

A common secondary structure in proteins where the polypeptide chain coils into a right-handed spiral, stabilized by hydrogen bonds

beta sheets

A secondary structure in proteins where polypeptide strands run parallel or antiparallel and are held together by hydrogen bonds

denaturing of a protein

known also as unfolding, which can occur due to chemical treatment or high temperatures, leading to possible loss of function, insolubility and unstable. if optimal conditions are returned, the protein can often refold and regain function.

importance of non-covalent bonds

very important for biological functions, because they are easily broken and reformed, they allow for dynamic interactions

globular proteins

hydrophobic residues are buried in a hydrophobic core containing nonpolar side chains (in an aqueous environment), while the outside of the protein has polar side chains which can form hydrogen bonds to water.

homodimer

composed of two identical polypeptide chains

heterodimer

consists of two different polypeptide chains

annealing

when complementary single-stranded nucleic acids come together by base-pairing

native state

a functional protein; not denatured.

disulfide bonds

found in the secondary and tertiary structures of proteins. They can occur within a single polypeptide chain (intramolecular) or between two polypeptide chains (intermolecular

hydrogen bonds

primarily found in both the secondary and tertiary structures of a protein; in secondary structures, they occur between the backbone atoms of the polypeptide chain, forming structures like alpha helices and beta sheets, while in tertiary structures, they can form between the side chains of amino acids

Element

a distinct type of substance or matter. each element has atoms that contain a unique number of protons in nucleus.

Atom

The fundamental unit of an element, made of protons, neutrons, and electrons.

Ion

An atom or molecule that carries a full charge —positive if it contains more protons than electrons, and negative if it contains more electrons than protons.

Molecule

A structure made of two or more atoms held together by covalent bonds.

Covalent Bond

An attraction between two atoms based on shared electrons.