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Homework/Test/Honors

Objectives:  Discuss how lipids play a role in protein folding and transport of proteins through the cell membrane

Standard: Structure, function, properties of phospholipids and lipids

Sub-objectives:  cell metabolism

Pose questions on:  How does the phospholipid bilayer of a cell membrane work?

Beyond genes: Lipid helps cell wall protein fold into proper shape

It takes more than the genetically coded sequence for a membrane protein to fold and function. Its LIPID environment also plays a role.

A protein that provides a vital passage through a bacterium’s outer cell wall will misfold and malfunction if that wall is built of the ‘wrong’ material, scientists at The University of Texas Medical School at Houston report in a finding that has long-term implications for understanding diseases caused by misfolded proteins such as cystic fibrosis, Alzheimer’s disease, and mad cow disease.

Professor of Biochemistry and Molecular Biology William Dowhan, Ph.D., and colleagues shows that PHOSPHOLIPIDS, which make up the permeable barrier of CELL membranes, play a direct role in the folding of membrane proteins – proteins that penetrate the membrane or bind to either side of it.

“What we’ve demonstrated again is that it’s not just a membrane protein’s genetically determined sequence that dictates how it folds so that it can function properly. Its lipid environment also plays a role,” Dowhan said. “People used to assume that specific lipids made no difference.”

Dowhan and colleagues looked at how a protein called GabP, which transports an AMINO ACID across the membrane of the bacterium E. coli, is affected by the presence of a phospholipid named phosphatidylethanolamine, or PE for short.

Phospholipids, unlike their FATTY ACID and CHOLESTEROL cousins, include a phosphate group that spurs them to form a bilayer with water-friendly outer layers sandwiching an impermeable water-unfriendly inner layer that defines the outer surface of cells. Transport of nutrients and waste material across the cell membrane is then governed by the specific proteins associated with it.

In a strain of E. coli lacking PE, the GabP protein misfolded, with two areas of the protein inverting from their normal structure. The PE-lacking protein’s amino acid transfer rate plummeted to nearly zero, falling 99 percent compared to the transfer rate in unaltered E. coli with PE.

GabP is the third membrane PROTEIN that Dowhan and colleagues have shown to be affected by the presence of PE.

The team is using the E. coli model to discover how all proteins fold in the membrane, not just transport proteins such as GabP but also biosynthetic proteins that manufacture complex compounds such as proteins and fats out of simple compounds.

“The next goal now that we’ve defined the phenomenon is to get into the specifics, find the mechanisms by which these proteins fold. What part of the protein interacts with the lipid, and what part of the lipid with the protein?” said Dowhan.

Understanding the molecular basis for membrane protein folding will help researchers address serious diseases caused by misfolded proteins. “In cystic fibrosis, Alzheimer’s disease and mad cow disease, the dysfunctional proteins are associated with membranes,” Dowhan said.

Membrane proteins make up 30 percent of known proteins. Another 40 percent are loosely tied to membranes. “So you are looking at possibly 70 percent of biology occurring at or in a lipid membrane surface,” Dowhan said.

Membranes and their surface proteins are accessible targets for pharmaceuticals, and most drugs target either membrane proteins on human cells or the membrane proteins of pathogens.

 

 

 

 

 

 

Honors

Instructions: Please number the lines in the article, highlight concepts and terms, and place notes along the margins. (5 pts.)

Questions

Please write answers to all the questions, except the multiple choice or fill in the blanks, on a separate sheet of paper and incorporate the question in your answers.

  1. Define and use all underlined words in a sentence. (5 pts.)
  2. Create a divided page graphic organizer study guide using the CAPITALIZED bold type words. (10 pts.) 
  3. Which type of molecules makes up the cell membrane?  Circle the best answer.  Cite the sentence and paragraph in the article, page in the textbook, or other source. (5 pts.)
    1. cellulose
    2. polysasccharides
    3. phospholipids
    4. triglycerides
  1. E. coli that lacked the PE phospholipid in its membrane had trouble ________________________. (5 pts.)
    1. synthesizing essential proteins
    2. transporting amino acids through the membrane
    3. blocking any proteins and pathogens from entering the cytoplasm
    4. holding the membrane bilayer from degenerating
  1. GabP is a ______________________.  (10 pts.)
    1. lipid
    2. protein
    3. sugar
    4. monosaccharide
    5. amino acid
  1. Draw and label a phosphate functional group. (10 pts.)

        7.   Which one of the following is not a characteristic of a phospholipid?  (10 pts.)

    1. Phospholipids have a glycerol attachment (backbone)
    2. Phospholipids have two fatty acid tails
    3. Phospholipids have a phosphate functional group attached to them
    4. Phospholipids have a hydrophilic “tail” and hydrophobic “head”
    5. Phospholipids are the main material in cell membranes
  1. Illustrate and explain how the phospholipids in a cell membrane are aligned, labeling the hydrophilic and hydrophobic parts of the phospholipid molecule. (15 pts.)

       9.   “Transport of nutrients and waste material across the cell membrane is governed by the specific proteins

              associated with it.  A protein that provides a vital passage through a bacterium’s outer cell wall will misfold 

             and malfunction if that wall is built of the ‘wrong’ material.”

             What are the implications of this statement regarding transport of materials in and out of a cell through the cell

             membrane?  In other words what do you think will happen to cells (and eventually to organisms) if something

             goes wrong or if something is missing in the cell membrane.  Cite the article to support your opinion.  (25 pts.)

 

All above questions must be answered before any extra credit will given for extra credit questions.

Extra Credit: (2 pts. each)

  1. What is an axon?
  2. What is meant by a permeable barrier?
  3. What is a pathogen?

Essay Extra Credit:  Cite all your sources (15 pts.) 

1.  Write a one page essay on either cystic fibrosis or Alzheimer’s disease.  Be sure to mention how protein transport might affect the disease.