0045 Cell membranes Transporters and trafficking Lecture 1
0045 Cell membranes Transporters and trafficking Lecture 1
0045 Cell Membranes Outline lecture content GDH 10 lectures Membrane transport Membrane protein trafficking PR W 10 lectures Structure and function of membrane lipids and proteins Exam after Christmas 80% of marks Essay to complete in 10 weeks 20% of marks
Write an essay on ‘Integral Membrane Proteins as Drug Targets’ 1500 words (not including figure legends or references) Many drug targets for human ailments, such as cancer, psychiatric/neurological disorders, immunological diseases and cardiac diseases, are membrane proteins. Membrane protein targets belong to many classes including ion channels, transporters, receptors (eg GPCR’s, RTK’s). We want you to research a topic with the title ‘Integral Membrane Proteins as Drug Targets’ and write an essay containing up to date information on this topic. We expect the essay to be well referenced, contain primary literature (i. e reference to and explanation of research articles) and have a good structure. You may choose a particular drug to write about (either one in clinical use or in development) or a particular protein (or class of protein) that is targeted by multiple drugs.
In your essay you should include: A general introduction to the topic (aimed at an informed, but not expert audience) The main content of the essay. A strong concluding paragraph, highlighting any concepts emerging from your consideration of the topic, and containing future perspectives. Examples of the types of issues you may want to address in the essay are: What is the disease/disorder that you are writing about and how does it manifest itself? How many people are affected by the condition/economic cost? Why is the membrane protein (class of proteins) a good drug target in combatting the disease in question? How was the drug developed? / How is it being developed? (ie rational design, screening). What is the normal function of the protein being targeted? What effect does the drug have on the protein? You may want to include experimental evidence to support mechanism of action of the drug. Does the drug have side effects and what are these? How does the drug compare to alternative treatments of the disease? NOTE: This is not a comprehensive list of issues you may want to address. All essays should be submitted electronically on Moodle as a Word document.
Aims: Overall aims of transporters and trafficking lectures: To introduce the principles and mechanisms involved in the transport of solutes across cell membranes. To introduce mechanisms involved in sorting and cell signalling regulated subcellular trafficking of membrane proteins.
Aim: 1 st two lectures: To describe distinguishing characteristics of nonmediated and mediated membrane transport
Kinetics of non-mediated transport J = D. ([S]o – [S]i) x Where J is the flux D is the diffusion coefficient, X is distance of diffusion [S]o – [S]i is the conc gradient D/x are usually lumped as P (for permeability)
Lipophilicity
Single site pores and channels Examples are ion channels, aquaporins etc. Similar to non-mediated diffusion in that there is usually a linear relationship between flux and concentration. Can distinguish between this pore type transport and lipid diffusion by use of specific pore blockers. Kinetically they often behave as single site pores and this is therefore different to facilitative transporters as these are thought to have two binding sites.
The GLUTs
Extended GLUT family GLUT 1 GLUT 3 Class I GLUT 4 GLUT 2 GLUT 5 GLUT 7 Class II GLUT 9 GLUT 11 GLUT 6 GLUT 8 GLUT 10 Class III GLUT 12 HMIT (GLUT 13) From: Joost and Thorens 2002
2 D structure of GLUT 1
GLUT 1 constructs
Summary and main points 1. Non-electrolytes enter cells via the lipid bilayer in proportion to their lipid solubility 2. Transporters and channels are membrane spanning proteins for specialised substrates 3. The GLUT family of sugar transporters are typical examples of proteins that exhibit catalysed (mediated /facilitated) transport
- Slides: 14