Problem A transmembrane protein has 1000 aa. The 5th aa is found on the external side of the cell membrane. It interacts with the aqueous environment outside the cell. Amino acid 90 is inside the membrane bilayer. Aa 100-600 are intracellular, and 200-400 make a tight ball with minimal exposure to the aqueous cytoplasm. Amino acid 979 is found on the extracellular side of the protein where it forms a weak ionic bond with Cl-.

a. Can you draw the protein and mark positions of all mentioned aa in it?

b. What are the properties of these amino acids? 

I dont necessarily want/need the exact answers to these questions, rather i would like some guidance in what principles i would need to understand and conceptualize to attack this problem. Thanks all !

  • $\begingroup$ Please read our homework policy. For questions like these, we want to see some effort from you in trying to answer your question(s), and then we can clarify/correct you from there. $\endgroup$ – MattDMo Sep 18 '14 at 21:43
  • $\begingroup$ @MattDMo Please do note, that he is NOT requesting answers. He needs help figuring out where and how to start :) $\endgroup$ – L.B. Sep 18 '14 at 21:45
  • $\begingroup$ Thank you L.B If there is anything more i need to add by all means please let me know. I would just like more knowledgable members to help me on the core "philosophy" to this. $\endgroup$ – Macedon93 Sep 18 '14 at 21:46
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    $\begingroup$ @Macedon93 It would be great if you could share some of your thoughts about this. It is easier to help people when you know where they got stuck. $\endgroup$ – Chris Sep 18 '14 at 21:49
  • $\begingroup$ Ok, I see that this problem is a test to my knowledge of membrane proteins, atleast that is what i am assuming at this point. I can assume that question A.) is referring to the protein connexin, which traverses through lipid bilayers. However not completely sure. What really stumps me is the jargon in the question, such as "1000 aa", and "Aa 100-600". $\endgroup$ – Macedon93 Sep 18 '14 at 21:54

I made a quick sketch on the basis of the information you gave (this is not to scale):

enter image description here

Aminoacid 5 (aa5) of the protein is on the outside, aa90 is inside the membrane. What we don't know here where the transmembrane part starts (directly with aa6 or later) and how it is organised (I indicated this as a transmembrane helix, but this can of course be different). Then we know that the border between the transmembrane part and the cytosolic part is somewhere between aa90 and aa100, that aa100 to aa200 seems to be some connecting part. The aa200 to aa400 is a globular domain which shields hydrophobic amino acids from the cytosol, so this part has to contain a high percentage of hydrophobic amino acids.

The part from 400 to 600 is again cytosolic but with no further information about the structure. After aa600 starts a second transmembrane part of the protein, but here we don't know how long it is. The maximum possibility would be until aa977, since we know the aa978 is outside of the membrane.

  • $\begingroup$ Thank you for your help. I followed your lead and my professor told me this is what she wanted to see, and with the help of shigeta, I now know how to illustrate this problem. However, what exactly tells you where aa5, aa90, aa200 etc are located ? What information are you basing its locations off of ? Or are you simply drawing a transmembrane protein, and labeling its respective amino acid sequences based off of common knowledge $\endgroup$ – Macedon93 Sep 19 '14 at 16:22
  • $\begingroup$ @Macedon93 No, I am going along the text you provided. As I said, this is a quick sketch, for a more detailed figure you need to have more information (for example where the transmembrane sections begin exactly and so on). I knew that aa5 is outside and aa90 in the membrane. I also knew for example the aa200-400 is globular. $\endgroup$ – Chris Sep 19 '14 at 18:22
  • $\begingroup$ Duh, so stupid i realize these were stated in the question. Thanks again ! $\endgroup$ – Macedon93 Sep 19 '14 at 18:35

Membrane proteins are usually drawn as topological digrams with two parallel horizontal lines representing the membrane. lines as 'extracellular' and below the lines as 'intracellular' for instance, but that is not what is being asked for here.

Its not clear to me that the number of transmembrane spans are fully described, nor are the boundaries of the transmembane spans. I think what is being asked for could be a domain diagram of the amino acid chain.

Draw a line on graph paper representing the peptide and use a scale to label each point described. For regions draw a box around the peptide line to describe a domain, and label it.

I think its hard to talk about amino acid properties other than hydrophilic/hydrophobic. hope this helps?

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    $\begingroup$ I think there's enough information given here to map out the protein. It probably starts on the external side, moves inside the cell, has a large cytoplasmic domain, then moves back out. The position and descriptions of the AAs also tell us something about their properties, even if it's subtle, such as "forms a tight ball with minimal surface exposure". The chloride ion interaction should also tell you something about charge. $\endgroup$ – user137 Sep 18 '14 at 23:39
  • $\begingroup$ Possibly, but if you had the full amino acid sequence, you would normally use a transmembrane domain algorithm. There could be three helices. Such mps are known. The problem is a pretty limited set of facts and it doesn't seem like you need to jump to any conclusions imho. $\endgroup$ – shigeta Sep 19 '14 at 6:43
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    $\begingroup$ Thank you for the insight. Illustrating this has become much more logical. Still have a decent way to go ! $\endgroup$ – Macedon93 Sep 19 '14 at 17:59

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