Lipid Modification

Question 1

how does lipidating a protein affect it?

Answer 1

may cause it to associate with the membrane; will help in subcellular localization; will regulate activity

Question 2

what is trypanosomiasis?

Answer 2

african sleeping sickness; parasitic disease caused by protozoa (trypanosoma brucei)–transmitted by then tsetse fly;

Question 3

symptoms of ASS?

Answer 3

high fever and headaches; CV problems; CNS issues–seizures, manic behaviour and excessive sleepiness; fatal if untreated

Question 4

how is ASS diagnosed?

Answer 4

blood is viewed under a microscope for the presence of the parasite

Question 5

transmission of ASS

Answer 5

fly bites animal or human already infected with trypanosomes; parasites travels to salivary glands of fly; fly goes and bites another mammal–>parasite injected into mammal;

Question 6

treatment for ASS

Answer 6

n-mysritsoyltransferase is essential for the survival of t. brucei–> inhibited NMT (take a pill with inhibitors)–>will inhibit our OWN NMT

Question 7

what is hutchinson-gilford progeria syndrome?

Answer 7

disease of rapid aging; growth retardation, hair loss, loss of subcutaneous fat and atherosclerosis; fragile bodies;–susceptible to heart attack/stroke

Question 8

what causes HGPS?

Answer 8

nuclear problem–abnormal nuclear lamina (highly invaginated)–> problem with protein called Lamin A–>not a smooth/round nucleus

Question 9

what is lamin A

Answer 9

composes the proteinaceous lamina layer beneath the nuclear membrane; provides structural support for the nucleus; regulation of gene expression, DNA replication, and cell division; participates in chromatin organization; anchors the nuclear pore complex embedded in the nuclear envelope

Question 10

what is wrong with lamin A in HGPS?

Answer 10

problem with its maturation; requires prenylation and then cleavage at the RSY-LLG motif to make proper lamin A; improper lamin A has had the recognition seq deleted so it remains permanently farnesylated–>interferes with the integrity of th lamellar envelope and irregularly shaped nuclei

Question 11

what is prenylation?

Answer 11

addition of a 15-C group (farnesyl) or a 20-C (geranylgeranyl)–>isoprenoid to protein via thioether bond; attachs to C-terminal cysteine (not every cysteine can be prenylated)–cysteine near the c terminus

Question 12

consensus seq for the prenylation of a cysteine

Answer 12

CaaX, where a = alipathic

Question 13

what is prenylation catalyzed by?

Answer 13

prenyltransferase

Question 14

isoprenoids are precursors of cholesterol

Answer 14

ya

Question 15

how is HGPS dealt with?

Answer 15

prevent accumulation of farnesylated lamin A–inhibit prenylationin mice; seems to ease blebbing

Question 16

what is huntington’s disease?

Answer 16

neurodegenerative disorder; caused by expasion of polyglutamine repeats in the huntintin protein –> far more glutamines in the mutant protein

Question 17

what is myristoylation of proteins?

Answer 17

addition of myristate (14:0) to the N-terminal glycine of a protien; targets protein to membranes, promotes reversible association with tehm (important for enzymatic activity); irreversble and cotranslational

Question 18

process of myristoylation

Answer 18

the Met is removed by methionyl peptidase; N-myristoyl transferase transfers myristate to N-terminal glycine

Question 19

glycine is essential for the myristoylation of a protein; even if alanine is on their (R= CH3) the protein cannot be myristoylated

Answer 19

ya

Question 20

how can the incorrect myristoylation cause cancer?

Answer 20

Src becomes abonormally activated; transforming activity (normal cell to cancer cell) associated with Src overactivity; when Src is on, interacting w membrane via N-myr, it targets cell to proliferate; however it can be turned off; there is a mutation in Src which causes it to always be on and thus always stimulate cel proliferation

Question 21

why does th N7 mutant not cause cancer?

Answer 21

contact inhibited–when they sense there’s not much room left, they stop proliferating–>N7 mutant had reduced myristoylation and the N7 mutant does not associate with the plasma membrane

Question 22

how can myristoylation inhibitors act as cancer therapy?

Answer 22

NMT inhibitor would prevent association of Src with membrane–>no cell proliferation

Question 23

prevelance of hutchinson-gilford progeria syndrome

Answer 23

1 in 4 million

Question 24

why is palmitoylation of membrane proteins important?

Answer 24

it brings domains closer together for their function

Question 25

calm palmitoylate the N or C terminus or middle of protein

Answer 25

ya

Question 26

how is huntington’s disease associated with lipid modification?

Answer 26

expansion of the polyQ region of huntingtin protein causes improper palmitoylation–>trafficking of h. protein to membrane is impaired; promotes aggregation and enhanced neural toxicity