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a. Processing
i. as it enters the __, the nascent polypeptide is acted on by __located within either the membrane or __of the RER
1. __ portion containing the signal peptide is removed from most nascent polypeptides by a __, the ssignal peptidase
- RER cistern
- enzymes
- lumen
- N-terminal
- proteolytic enzyme
-
a. __are added to the nascent protein by the enzyme __
i. both the __ ande __ are integral membrane proteins associated with the __that act on nascent proteins as they enter the __
- carbs
- oligosaccharyltransferase
- signal peptidase and oligosaccharyltransferase
- translocon
- ER lumen
-
i. the RER is a major protein processing plant and is packed with molecular __that recognize and bind to __ or __ and give them the opportunity to attain their correct 3D structure
1. the Er lumen also contains a number of __, such as __
- chaperones
- unfolded or misfolded proteins
- protein-processing enzymes
- protein disulfide isoemrase
-
i. proteins enter the ER lumen with their __ in the __state, but they leave the compartment with may of these residues joined to one another as __
1. the formation and rearrangement of __ bonds is catalyzed by __
- cysteine residues
- reduced
- oxidized disulfides
- disulfide
- PDI
-
a. disulfide bonds play an important role in __ that are present at the extraceullular surface of the plasma membrane or secreted into the extracellular space
maintaining the stability of proteins
-
i. the ER is constructed for its role as a __ for the __ of the cell
1. its membrane provides a __ to which many __can attach
a. the __of the __ provides a specialized local environment that favors the __, __, and __ of a selected subset of the cell’s proteins
- port of entry
- biosynthetic pathway
- large surface area
- ribosomes
- lumen
- ER cisternae
- modification, folding, and assembly
-
1. the segregation of these newly synthesized proteins in the __ removes them from the cytosol and allows them to be __ and __ toward their ultimate destination, whether outside the cell or within one of the cytoplasm’s membranous organelles
- ER cisternae
- modified and dispatched
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a. Synthesis of Integral Membrane Proteins on Membrane-Bound Ribsomes
i. integral membrane proteins—other than those of the mitochondria and chloroplasts—are also synthesized on __
1. these membrane proteins are translocated into the __ as they are synthesized using the same machinery described for the synthesis of secretory and lysosomal proteins
- membrane-bound ribosomes of the ER
- ER membrane
-
a. unlike __ and __, which pass entirely through the ER membrane during __, __ contain one or more __ that are shunted directly from the channel of the __into the lipid bilayer
- soluble secretory and lysosomal proteins
- translocation
- integral proteins
- hydrophobic transmembrane segments
- translocon
-
i. as a polypeptide passes through the __, it is proposed that this __ in the channel continually opens and closes, which gives each segment of the nascent polypeptide an opportunity to __itself according to its __properties into either the aqueous compartment within the __ or the surrounding __ of the lipid bilayer.
- translocon
- lateral “gate”
- partition
- solubility
- translocon channel
- hydrophobic core
-
1. those segments of the nascent polypeptide that are __will spontaneously “__” into the lipid bilayer and become __ of an integral membrane protein
a. this concept has received strong support from an in vitro study in which __were given the opportunity to translocate custom-designed nascent proteins that contained test segments of varying __
- hydrophobic
- dissolve
- transmembrane segments
- translocons
- hydrophobicity
-
The more hydrophobic the test segment, what?
the greater the likelihood it would pass through the wall of the translocon and become integrated as a transmembrane segment of the bilayer
-
i. __ membrane proteins can have an orientation with their __ facing either the cytosol or the lumen of the ER
1. the most common determinant of membrane protein alignment is the presence of __ flanking the __end of a __segment
- single-spanning
- N-terminus
- positively charged amino acid residues
- cytosolic
- transmembrane
-
1. during the synthesis of membrane proteins, the inner lining of the __is thought to orient the nascent polypeptide so that the more __end faces the __
-
i. In multispanning proteins, sequential transmembrane segments have __
their arrangement within the membrane is determined by the __
- opposite orientations
- direction in which the first transmembrane segment is inserted
-
1. once determined, every other transmembrane segment has to rotated __before it can exit the translocon
a. suggestion: a translocon, by itself, is capable of what?
- 180o
- properly orienting transmembrane segments
-
i. it is more than a simple passageway through the ER membrane; it is a complex machine capable of __and performing complex mechanical activities
recognizing various signal sequences
-
a. Membrane Biosynthesis in the ER
i. membranes don’t arise as __, but from __ that grow as new proteins and lipids are inserted
ii. membrane components move from the __to virtually every other compartment in the cell
- new entities from pools of protein and lipid that mix together
- preexisting membranes
- ER
-
1. as the membrane moves from one compartment to the next, its proteins and lipids are __
a. these modifications contribute to giving each membrane compartment a __ and __
ii. Cellular membranes are __: the two phospholipid layers of a membrane have different compositions
- modified by enzymes that reside in the cell’s various organelles
- unique composition and distinct identity
- asymmetric
-
1. the asymmetry is established by the __ and maintained as __
a. domains situated at the __surface of the ER membrane can be identified on the __ surface of __, the __surface of __, and the __ surface of the __
- ER
- membrane carriers bud from one compartment and fuse to the next
- cytosolic
- cytosolic
- transport vesicles
- cytosolic
- Golgi cisternae
- internal
- plasma membrane
-
i. domains situated at the __ of the ER membrane maintain their __and are found at the __ of the plasma membrane
1. including its high __and abundance of proteins with __ and __, the lumen of the ER is a lot like the __
- luminal surface
- orientation
- external surface
- calcium concentration
- disulfide bonds
- carb chains
extracellular space
-
i. Most __ are synthesized completely within the ER except for __ (synthesis begins in __and is completed in __) and some unique __ of the __ and __ membranes, which are synthesized by enzymes that reside in those membranes
1. the enzymes involved in the synthesis of __ are integral proteins of the ER memrbaen with their __ facing the __
- membrane lipids
- sphingomyelin and glycolipids
- ER
- Golgi
- lipids
- mitochondrial and chloroplast membranes
- phospholipids
- active sites
- cytosol
-
a. newly synthesized phospholipids are inserted into the __of the bilayer facing the cytosol
i. some of these are __ into the opposite leaflet through the action of enzymes called __
lipids are carried from the __ to __ and __ as part of the __ that makes up the walls of __
- half
- flipped
- flippases
- Er to Golgi and plasma membrane
- bilayer
- transport vesicles
-
i. membranes of different organelles have markedly different __composition, which indicates that what happens?
- lipid
- changes take place as membrane flows through the cell
-
several factors may contribute to such changes
The first?
a. meost membranous organelles contain enzymes that modify lipids already present within a membrane, converting one type of phospholipid to another
-
several factors may contribute to such changes
The second?
a. when vesicles bud from a compartment, some types of phospholipids may be preferentially included within the membrane of the forming vesicle, while other types may be left behind
-
several factors may contribute to such changes
The third?
a. cells contain lipid-transfer proteins that can bind and transport lipids through the aqueous cytosol from one membrane compartment to another
-
i. these proteins facilitate the movement of specific __from the __to other organelles without the involvement of __
1. __ is thought to occur at sites where the ER comes into __ to the outer membrane of other organelles
- lipids
- ER
- transfport vesicles
- lipid transfer
- very close proximity
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