MBB201 topic 4 proteins

sturcture levels of proteins

primary:amino acid sequience, secondary: stable arranglemennts of amino acids, tertiary sturcture: folded structure of peptide, quaternary structure: arangment of multiple peptides

what are the 5 categories of r groups

nonpolar(hydrophobic), polar, uncharged, acidi, and basic

alpha helix properties

1.alpha helix - spiral shape, peptide backbone, r groups face outwards, 3.6 residues/turn, stabilized by h bonds, h bonds between every fourth amino acid, linking c=o of one peptide to the n-h of another, a helices can by hydrophobic or philic, can be right or left handed,

how do r groups affect a helix stability

electrostatic or steric interaction between adjacent side chains 3-4 residues away can affect the stability of an a helix

whats two molecules usually aren’t found in alpha helices?

1.proline- the nitrogen of proline is in a rigid ring which intereres sterically with th ebackbone, proline in a peptide bond lacks an amid hydrogen to form hydrogen bonds(helix breaker) 2.glycine - very flexible, allows for conformations that do not suit alpha helices , glycine is so small that it annot protect the backbone hydrogen bonds from the aqueous environment

how do side chains affect protein localization

amphiphatic helices: one side is hydrophobic, the other is hydrophilic, allows membrane associateion, helices with a region of hydrophobic residues flanked by hydrophilic residues can allow membrane spanning

what are beta sheets

-the form rigid structures at the core of many proteins, theyre composed of beta strands, and stabilized with interstrand hydrogen bonds, beta sheets can be anti parallel or parallel depending on relative orientation of the strands, arroes always point towards c terminus

what are the properties of beta sheet properties

-can be twisted, the R groups are perpendicular from the plane of the sheet, the beta sheets are generally not found to be transmembrane, unless they are part of a beta barrel structure, hydrophobic side chains line the outer surface of the beta barrel, common in thransmembrane channel proteins

whats the protein tertiary structure

3d arangement of all atoms in a protein, generated by the folding and packing of secondary structure elements usually stabilized by non covalent interactions, usually between r groups or r groups and backbones rather than H bonding between c=o and n-h of the backbone

what noncovalent interactions helpwith protein folding

1.hydrogen bonds 2. vanderwaals interactions 3. electrostatic interactions, 4. hydrophobic interactions

what are disulfied bonds

theyre the covalent bonds that can also help stabilize a proteins conformation, theyre very very strong, they dont form in the cytosol becasue of the high concentration of reducing agents , the can only form between two cysteine side chains in proteins

whats quaternary structure

referes to protein complexes with more than one polypeptide chain, each indiv. polypeptide chain in the protein is called a subunit, the level of organization concerned with subunit interactions and assembly, bonds and forces maintaining quaternary structure are the same as those responsible for tertiary structure

what are protein domans

• distinct, stable, structural units that often have separate functions asn fold as independent compact units, they can move as a single entity with respect to the entire protein, one domain is typically made of a single stretch of primary sequence, proteins may have on or more domains, proteins with similar functions often share a common domain

whats an example of how different domains of a protein are often associated with different functions

src kinase - an important signaling protein, possesses four functional domains, each with a different function, each domain is made from the same single stretch of primary sequence

what are fibrous proteins

dominated by single repeating element of secondary structure (highly ordered), possess properties that give strength and or flexibility important for structural functions (ex alpha keratin, silk elastin, collagen)

globular proteins

most proteins are globular proteins, roughly spherical in shape and often contain several types of secondary structure (ex myoglobin, lysozyme, cytochrome c)functions : enzymes, motor proteins, regulatory proteins

waht is alpha keratin

• a fibrous protein, right handed helix, coiled coil composed of two alpha keratin chains is left handed

whats a native state

the most stable conformation that a protein tends to fold in

what is denaturation

disrutpion of the native struture of a protein by breaking the weak bonds responsible for 2 and 3 degree structures

casues of protein denaturation

temp change, extrene ph, detergents and organic sovents, urea or guanidinium chloride, reducing agents

whats a chaperone protein

help some eptides to fold into their final conformation, some bind to newly synthesized or paritally folded chains and help them fold, others form isolation chambers which prevents the polypeptide chain from aggregating with either other molecules or itself in the cytoplasm.

what diseases could arise from the misfolding of proteins

alzheimers disease, huntingtons, creutzfeld jakob disease, mad cow disease

why are some parts of a protein in intrinsically disordered sequences bc they have functional importance such as binding, scaffolding, tethering, and flexibility

whats a protein family

a group of proteins where each member has an amino acid sequence and 3d conformation that closely resembles each other, they arise over time during evolution (ex: elastase and chymotrypsin, members of the serine protease family, despite their similarity they differe in the substreate specificity, they cleave to different proteins )

whats a binding site

a region of protein that associates with a ligand, formed by a specific arrangement of amino acid side chains that may not be immediately adjacent to one another in thepolypeptied chain, the specific interactions between the binding site amino acids and the ligand dictates specificity

what are antibodies

y shaped molecule composed of two heavy chains and two light chains, the bind specifically to a target molecule called an antigen

what are enxymes

biological catalysts that speed up the rate of reactio byreducing the activation energy, they bind to substrates to for an enxyme substrate complex, afte the rxn has proceeded the enxyme will be in contact with the product as an unzyme produc complex and will eventually release a product

whats lysozyme

an enxyme that severs polysaccharide chains that form cell walls in bacteria, helps perform a hydrolysis reaction, helps the reaction overcome the activation energy, multiple non covalent interactions are formed inducing a strained conformation in one of the monosaccharieds to make it resemble a transition state

steps in the transition state

1. enzyme binds to two substrate molecules and orients them precisely to encourage a rxn to occur between them 2. binding of substrate to enxzyme rearranges electrons in the substrate creatin partial positive and negative charges that favour a rxn 3, enxyme strains the boudn substrate molecule forcing it toward a trasition state to favour a rxn

whats retinal

binds to the protein rhodopsin, retinal changes shape upon absorption of a photon

whats heme

it binds to the protein hemoblobin and allows reversible binding of oxygen

what are the levels of control for a protein

-regulation of gene expression, regulation of protein degredation, -confining proteins to specific comopartments - regulating protein activity directly

what are allosteric proteins,

proateins that can exist in two or more slightly different conformations, thir activity can be regulated by a shift from one conformation to the other

how do allosteric proteins change from one conformation to the other

the binding of a molecule to a site other than the catalytic site

how would the chang einconformation affect the function of the protein?

changing conformation may affect ability of the protein to bind a ligand or affect the activity of teh protein if it is an enzyme, they can bind inhibitors and activators.

positive regulation

binding makes it more active

protein kinase

enzyme that catalyzes the addition of a phosphate (phosphorylation- it can either activate or inhibit protein activity)

protein phosphatase

enxyme that catalyzes the removal of a phosphate (dephosphorylation)

phosphorylation

involves the enzyme catalyzed transfer of the terminal phosphate of atp to the hydroxyl group of serine, threonin or tyrosine, can also create docking site, its important for intracellular signaling proteins and the binding of a signla causes phosphorylation of tyrosine residues which allows other proteins to bind

what other covalent modifications can be made that can control the location and interaction of a given protein

-addition of an acetyl group, - attaching (poly odr mono) ubiquitin, -addition of fatty acids,

GTp vs GDP

for some proteins the phosphate is transferred from GTP instead of ATP, GTP-on, GDP-off

what are motor proteins

generate forces responsible for muscle contractions and most other eukaryotic cell movement

what are protein machins

proteins often work in tandemwith other proteins to function as a large multiprotein complex, hydrolysis of nucleoside triphosphates drives an ordered series of conformational changes in individual subunits which ultimately affects the entire complex (ex DNA replication, protein synthesis, vesicle budding, transmembrane signaling etc)