Using the active model for Niemann-Pick C1, the structure of the sterol-binding pocket, and the interaction involved in cholesterol binding should be described. Concept Introduction: Niemann-Pick C1 protein (NPC1) is a endosomal membrane protein required for transport of LDL derived cholesterol into cells. NPC1 consists with a sterol sensing domain (SSD) which is similar to SSDs in protein responsible for cholesterol biosynthesis, uptake and signaling. NPC1’s SSD forms a cavity that is accessible from both luminal bilayer leaflet and the endosomal lumen. According to the computational modeling, it is suggested that this cavity is large enough to be occupied by one cholesterol molecule. Cholesterol is transported as cholesterol esters which are packed in lipoproteins such as low density lipoproteins (LDL). LDL is transported to endosomes and lysosomes and they are subjected to lipolysis by lipase. Then released cholesterol is bound one molecule at a time to soluble intraliposomal protein, Niemann-Pick C2 (NPC2). NCP2 bound cholesterol is then transferred to another pocket in N-terminal domain of NPC1. Here the cholesterol is bound in opposite orientation. N terminal domain of NPC1 is connected via a proline rich region to transmembrane segment 1 (TM1).

Question

Want to see the full answer?

Answer 1

Question

Chapter 24, Problem 23P

Interpretation Introduction

Interpretation:

Using the active model for Niemann-Pick C1, the structure of the sterol-binding pocket, and the interaction involved in cholesterol binding should be described.

Concept Introduction:

Niemann-Pick C1 protein (NPC1) is a endosomal membrane protein required for transport of LDL derived cholesterol into cells. NPC1 consists with a sterol sensing domain (SSD) which is similar to SSDs in protein responsible for cholesterol biosynthesis, uptake and signaling. NPC1’s SSD forms a cavity that is accessible from both luminal bilayer leaflet and the endosomal lumen. According to the computational modeling, it is suggested that this cavity is large enough to be occupied by one cholesterol molecule.

Cholesterol is transported as cholesterol esters which are packed in lipoproteins such as low density lipoproteins (LDL). LDL is transported to endosomes and lysosomes and they are subjected to lipolysis by lipase. Then released cholesterol is bound one molecule at a time to soluble intraliposomal protein, Niemann-Pick C2 (NPC2). NCP2 bound cholesterol is then transferred to another pocket in N-terminal domain of NPC1. Here the cholesterol is bound in opposite orientation. N terminal domain of NPC1 is connected via a proline rich region to transmembrane segment 1 (TM1).

Expert Solution & Answer

Want to see the full answer?

Check out a sample textbook solution

See solution

Students have asked these similar questions

carbons in each of the structures below. For instance, the central carbon of chloromethylbutane (pictured 3. A chiral carbon is a carbon that is single-bonded to four different types of groups. Identify the chiral above) is a chiral carbon. (Can you see how the groups attached to it are all chemically different?) In each of the chiral molecules below, identify all the carbons that are chiral carbons by drawing a circle around each one of them. (a) the carbohydrate glucose H O (b) the carbohydrate fructose CH₂OH 1C H-C-OH 3 HO-C-H 4 H-C-OH 5 H-C-OH 6CH₂OH D-Glucose (linear form) (c) the amino acid leucine O O H3C. HO H H- -OH CH 3 NH2 H- -OH CH₂OH OH

We always include controls in the Annexin-V-GFP/Propidium Iodide flow cytometric assay to study apoptosis. List four types of controls in this assay. Why do we need these controls? Explain your answers. After the flow assay, if we like to examine the morphology of the viable, early apoptotic and late apoptotic cells by confocal microscopy, what can we do and what are the expected results?

3. (2 points) Your lab partner accidentally used a pen instead of a pencil to mark the baseline and label the lanes of their TLC plate. Briefly (1-2 sentences for each point) describe (a) what would happen to the ink when you develop the TLC plate; and (b) how this would affect the experiment. 1