Lecture 4 Flashcards

Question

what are KMTs and KDMs

Answer 1

lysine methyltransferases = KMTs lysine demethylases = KDMs

Answer 2

consequences for transcription and dna repair mechanisms like phosphorylation, acetylation and methylation provide new binding sites for proteins Specific domains bind Ac-Lys, Me-lys, Me-arg and surrounding sequences play an important role in transcription regulation

Answer 3

regulation of transcription chromatin and dna repair

Answer 4

when protein folded

Answer 5

folded structure depends on hydrophobic interactions in the interior of the structure polar side chains found on outer surface

Answer 6

completely folded conformation of a protein functional conformation of a protein

Answer 7

usually after folding is complete

Answer 8

polar = can bond with other proteins and make soluble, far away comes together hydrophobic interactions = many, strong h bonds = many, moderate van der waals interactions = many, weak ionic bonds = few, v strong, since only 5 aas disulfide bonds = few, very strong covalent, since only 1 aa

Answer 9

stabilize secondary structures -- involve peptide bond= backbone

Answer 10

hydrophobic interactions between secondary structures form the tertiary structures --> involve side chains

Answer 11

primary sequence of aa

Answer 12

state of minimal energy - folding is thermodynamically favoured = ΔG neg, free energy, lower than that 0, that of primary structure, see if active

Answer 13

can be spontaneous in principle but assisted by diff biological mechanisms

Answer 14

complex process - diff free energy conformations unfolded (denatured) domains have extended conformations with no secondary or tertiary structure folding proceeds through intermediates that have increasing structure to native state

Answer 15

primary = very flexible, moves a lot, flexibility of alpha carbons secondary = less flexible native state = one structure usually, folding goes through intermediate states

Answer 16

native state is most stable conformation of protein native state can be in eq with near native folding intermediates

Answer 17

hydrophobic contacts - exclusion of water faces interior of protein

Answer 18

NOOO some domains need a ligand partner to be stable cofactor (haem, steroid, etc) or another protein subunit

Answer 19

get closer together in structure native state can be in eq - stabilized with an intermediate state

Answer 20

have some secondary structure, but tertiary structure incomplete some hydrophobic side chains exposed instead of buried more of the polypeptide is flexible and disordered

Answer 21

hydrophobic regions prefer to be in contact with others Interaction between diff unfolded proteins leads to insolubility fried egg

Answer 22

intermediate - some regions hydrophobic residues face water = high risk aggregation, salvation cages, makes protein v unstable, if other proteins close = aggregates and misfolded proteins when native state = all in right state, not as risky for misfolding

Answer 23

leads to incompletely folded proteins immediately after protein synthesis = needs time to fold if require ligand not available - like cofactor = hydrophobic residues visible

Answer 24

genetic mutations harmful environmental conditions aging also the require ligand thing

Answer 25

leads to misfolded proteins and disease eg - sickle cell anemia and cystic fibrosis

Answer 26

eg heat, like global warming too leads to unfolding and misfolding of properly folded proteins

Answer 27

descrease efficiency of protein quality control mechanisms --> loss of protein homeostasis --> harmful aggregates of a misfolded protein eg amyloid --> neurodegeneration (Alzheimer, parkinsons, als, dementia)

Answer 28

can lead to changes in polypeptide sequences = aa substitution, indels, premature stop (cannot achieve native state) allelic variations sometimes cause genetic disease

Answer 29

sub to similar aa = may have little or not effect sub that greatly changes aa properties = can disrupt folding or function of protein similar = maybe nothing divergent = maybe cannot fold, so bad ex = phe to ser and ser to leu = both pathogenic asp to asn = not pathogenic

Answer 30

crowded environments= 10^5 - 10^6 total mrnas and 10^10 total proteins so lots of pressure to fold properly have help with chaperones = hold them and helps them fold

Answer 31

proteostasis refers to an extensive network of components that acts to maintain proteins in the correct concentration, conformation, and subcellular location, to cooperatively achieve the stability and functional features of the proteome

Answer 32

center of protein quality control network not part of native state tho molecular chaperones assist folding and prevent aggregation

Answer 33

hydrophobic residues showing so chaperones protect and once full protein is out = folds, maybe with help if aggregates = chap can help refold sometimes only way is to degrade protein= proteasome

Answer 34

exposed hydrophobic regions of folding intermediates, since should be on inside

Answer 35

Constitutively expressed essential under non stress conditions

Answer 36

heat shock proteins = HSPs temp goes ip and need more proteins to stop aggregates high expressed after stress eg = HSP70 is the 70kda HSP

Answer 37

covalently add a functional group to a side chain modifying the functional interactions of a protein are important for several cell functions like signalling and metabolism reversible and used as a switch

Answer 38

Determined by aa sequence and their hydrophobic and noncovalent interactions polypeptide chains transition over several intermediate folding structures before acquiring native stage = stage of minimal energy, protein folding is spontaneous

Answer 39

families of proteins assist in cellular protein folding and provide protein quality mechanisms to ensure homeostasis and avoid protein misfolding/aggregation Constitutively expressed and essential under non stress conditions