Molecular Biophysics I
2005
Session #5
"Molecular Chaperones"
(and 'other' chaperones)
February 23, 2005
BioMed 205/207
1:00 p.m. - 3:50 p.m.
"Over the past decade, the pendulum has swung from the norm being disbelief in molecular chaperones as important in protein maturation in vivo, toward a view that molecular chaperones are required for each and every step of the life of each and every protein." 1
The origin of the terminology 'molecular chaperone', and development of the more general concept, goes back to the late 1970's. Since that time the 'chaperone' literature has expanded mightily; however, the Medline citations for 'chaperone' now number in excess of 6000, while usage of the combined term 'molecular chaperone' occurs less frequently, with slightly more than 2000 citations. Is this difference significant? Is there a real distinction between a 'molecular chaperone' and some other kind of 'chaperone'? What, exactly, is a 'molecular chaperone'? What is a 'chaperonin'?
As with any field in biology, the scope of the involvement of a newly discovered protein, or even class of proteins, cannot be foreseen at the outset; thus, archaic terminology is carried along, the original definition of terms must be expanded to allow for newer discoveries, and inevitably the original meaning of the terms becomes blurred. Such is the case with 'molecular chaperone'. Accordingly, in this session, we shall consider:
Development of the field of molecular chaperones, as seen through the eyes of one of its pioneers, R. John Ellis;
The attempt to codify, or specifically define the term 'molecular chaperone', in order to distinguish it from other, similar, terminology;
Properties common to all molecular chaperones; features unique to molecular chaperones of a given 'class' or family;
The paper by PL Clark, who attempts to rationalize folding events in vivo in terms of the folding funnel;
Some broader biological implications of the role of molecular chaperones, i.e., beyond their specific role in protein folding and unfolding (e.g., in the aging process; in the development of certain diseases).
Specific references for this session are listed below. Note that Refs. # 1 & 2 are papers from our course general review list; for this session, we'll concentrate only on those sections identified below. A scanned version of Ref. #4 has been posted to the course page on the Library ERes site; alternatively, a html version is available through the Library's Ovid database [Journals@Ovid Full Text ].
Student Assignments:
The paper by Shtilerman et al, left over from last session: Student #10
ALL STUDENTS: No individual allocation of the refs for this session; we shall discuss all of them in class.
In addition, as alluded to above, the literature now contains many references to "other" chaperones, i.e., terminology containing words other than 'molecular' in association with the word 'chaperone'. See how many of these other terms you can discover, along with a brief explanation of what the terms mean. We'll then construct a chart of the type shown below to classify these 'other' chaperones.
| "Other" Chaperone | Reference | Nature of Chaperone |
Nature of Substrate |
|
|
1. Walter, S. and Buchner, J. Molecular chaperones - Cellular machines for protein folding. Angewandte Chemie-International Edition, 41: 1098-1113, 2002. [Sections 1.2 & 1.3; also, section 3]
2. Mogk, A., Mayer, M.P., and Deuerling, E. Mechanisms of protein folding: Molecular chaperones and their application in biotechnology. Chembiochem, 3: 807-814, 2002. [Sections 3, 4, & 6]
3. Ellis, R.J. From chloroplasts to chaperones: how one thing led to another. Photosynthesis Research, 80: 333-343, 2004.
4. Agard, D.A. To fold or not to fold. Science, 260: 1903-1904, 1993.
5. Clark, P.L. Protein folding in the cell: reshaping the folding funnel. Trends Biochem. Sci., 29: 527-534, 2004.
6. Soti, C. and Csermely, P. Chaperones come of age. Cell Stress & Chaperones, 7: 186-190, 2002.
1 J. L. Johnson and E. A. Craig, Cell 90: 201-204, 1997