membrane structure and function 2

Question 1

what is primary structure

Answer 1

polypeptide chain formed by covalent bonds

Question 2

what is secondary structure

Answer 2

regular folded form, often stabilized by H bonds, eg helices and beta pleated sheets

Question 3

what is tertiary structure

Answer 3

overall 3D structure stabilised by H bonds, hydrophobic, ionic, vdw forces, and sometimes disulphide bonds - combines secondary structures eg 7 helices of the TM domain

Question 4

what is quaternary structure

Answer 4

polypeptides going into assemblies.

Question 5

what is an alpha helix

Answer 5

single continuous structure, H bonds betweem every 4TH AA

Question 6

what are beta pleated sheets

Answer 6

H bonds between adj Beta strands, connected by long loops (parallel arrangement) or short loopd (antiparallel arrangement)

Question 7

where do H bonds occur in the polypeptide backbone

Answer 7

between COO- and NH3+

Question 8

what goes wrong functionally/structurally if proteins are misfolded

Answer 8

function almost always lost; misfolded proteins have a tendency to self associate and aggregate

Question 9

examples of aggregates caused by misfolded proteins

Answer 9

amyloid beta - alzheimers
prion protein
islet amyloid polypeptide IAPP in T2DM
——————————————
other misfolded proteins result in cellular processing that lead to their degradation eg CF

Question 10

You WON’T BELIEVE these 6 reasons why proteins can misfold - number 4 will BLOW YOUR MIND!

Answer 10

1. Somatic mutations - protein unable to adopt native folding
2. Translational/Transcriptional error leading to production of modified proteins unable to fold properly
3. failure of folding machinery
4. mistakes in posttranslational mods or in trafficking proteins
5. structural mod produced by environmental changes
6. induction of other protein misfolding by seeding and cross seeding

Question 11

what the frick is the amyloid hypothesis

Answer 11

accumulation of abnormally folded amyloid beta protein in the brain - amyloid beta (Aβ) is a short peptide & abnormal proteolytic byproduct of the TM protein amyloid precursor protein (APP) - function unclear.

Question 12

what is the structure of Abeta

Answer 12

soluble, largely alpha helical

Question 13

most common cause of CF

Answer 13

Phe deletion at residue 508 of CF TM conductance regulator (CFTR)

Question 14

what does CF508del lead to

Answer 14

misfolding of the protein whilst still in the ER

Question 15

what happens when the misfolded protein is recognised by the right cellular machinery

Answer 15

ubiquitinisation, trafficking to the proteosome, and degradisation

Question 16

what are prions

Answer 16

misfolded proteins (PrPSC) that interact with other normal proteins (PrPC), inducing misfolding of the normal protein and polymerisation