3 Notes
1. Despite being arbitrary, the choice of (at most) five consecutive
a.a. to identify small loops is due to the large number of small
homodimers that have been found to share such a structural
feature (see comments on Fig. 2a).
2. Originally [5] Q n was based exclusively on those (n) a.a. lying at
the interface Q n ¼
n
R
n
N
À
), according to the crystallographic
data. However, including also residues of small loops (i.e.,
not necessarily at the interface, but close enough) resulted in
a more incisive classification of homodimers.
3. The 50 dimers selected for this study have been preferentially
chosen among those whose stabilization energy of folding is
reported in literature (from equilibrium and/or kinetic unfolding measurements, see Table 1) [4, 7, 9].
4. A classification of the homodimers such as that reported in
Table 1 is essentially based on “average” values. The heterogeneity of tri-dimensional structures that protein may assume
makes this task hard sometimes because the two parameters
chosen to identify the main class of assignation may not go in
the same direction. An a posteriori check can be made using a ttest (easily performed on line or with most of the graphic
packages commercially available) that provides more rigorous
criteria of assignment. Such procedure has been used, for
instance, in the construction of Table 1.
References
1. Luque I, Leavitt SA, Freire E (2002) The linkage
between protein folding and functional cooperativity: two sides of the same coin? Annu Rev
Biophys Biomol Struct 31:325–356
2. Cornish-Bowden A (2014) Understanding allosteric and cooperative interactions in enzymes.
FEBS J 281:621–632
3. Koshland DE Jr (1959) Enzyme flexibility and
enzyme action. J Cell Comp Physiol
54:245–258
4. Mei G, Di Venere A, Rosato N, Finazzi-Agro ` A
(2005) The importance of being dimeric. FEBS
J 272:16–27
5. Di Paola L, Mei G, Di Venere A, Giuliani A
(2016) Exploring the stability of dimers through
protein structure topology. Curr Protein Pept
Sci 17(1):30–36
6. Neet KE, Tim DE (1994) Conformational stability of dimeric proteins: quantitative studies by
equilibrium
denaturation.
Protein
Sci
3:2167–2174
7. Rumfeldt JAO, Galvagnion C, Vassall KA,
Meiering EM (2008) Conformational stability
and folding mechanisms of dimeric proteins.
Progress Biophys Mol Biol 98:61–84
8. Kim TH, Mehrabi P, Ren Z, Sljoka A, Ing C,
Bezginov A, Ye L, Pome `s R, Prosser RS, Pai EF
(2017) The role of dimer asymmetry and protomer dynamics in enzyme catalysis. Science 355:
eaag2355
9. Marianayagam NJ, Sunde M, Matthews JM
(2004) The power of two: protein dimerization
in biology. Trends Biochim Sci 29:618–625
88
Giampiero Mei et al.
1. Despite being arbitrary, the choice of (at most) five consecutive
a.a. to identify small loops is due to the large number of small
homodimers that have been found to share such a structural
feature (see comments on Fig. 2a).
2. Originally [5] Q n was based exclusively on those (n) a.a. lying at
the interface Q n ¼
n
R
n
N
À
), according to the crystallographic
data. However, including also residues of small loops (i.e.,
not necessarily at the interface, but close enough) resulted in
a more incisive classification of homodimers.
3. The 50 dimers selected for this study have been preferentially
chosen among those whose stabilization energy of folding is
reported in literature (from equilibrium and/or kinetic unfolding measurements, see Table 1) [4, 7, 9].
4. A classification of the homodimers such as that reported in
Table 1 is essentially based on “average” values. The heterogeneity of tri-dimensional structures that protein may assume
makes this task hard sometimes because the two parameters
chosen to identify the main class of assignation may not go in
the same direction. An a posteriori check can be made using a ttest (easily performed on line or with most of the graphic
packages commercially available) that provides more rigorous
criteria of assignment. Such procedure has been used, for
instance, in the construction of Table 1.
References
1. Luque I, Leavitt SA, Freire E (2002) The linkage
between protein folding and functional cooperativity: two sides of the same coin? Annu Rev
Biophys Biomol Struct 31:325–356
2. Cornish-Bowden A (2014) Understanding allosteric and cooperative interactions in enzymes.
FEBS J 281:621–632
3. Koshland DE Jr (1959) Enzyme flexibility and
enzyme action. J Cell Comp Physiol
54:245–258
4. Mei G, Di Venere A, Rosato N, Finazzi-Agro ` A
(2005) The importance of being dimeric. FEBS
J 272:16–27
5. Di Paola L, Mei G, Di Venere A, Giuliani A
(2016) Exploring the stability of dimers through
protein structure topology. Curr Protein Pept
Sci 17(1):30–36
6. Neet KE, Tim DE (1994) Conformational stability of dimeric proteins: quantitative studies by
equilibrium
denaturation.
Protein
Sci
3:2167–2174
7. Rumfeldt JAO, Galvagnion C, Vassall KA,
Meiering EM (2008) Conformational stability
and folding mechanisms of dimeric proteins.
Progress Biophys Mol Biol 98:61–84
8. Kim TH, Mehrabi P, Ren Z, Sljoka A, Ing C,
Bezginov A, Ye L, Pome `s R, Prosser RS, Pai EF
(2017) The role of dimer asymmetry and protomer dynamics in enzyme catalysis. Science 355:
eaag2355
9. Marianayagam NJ, Sunde M, Matthews JM
(2004) The power of two: protein dimerization
in biology. Trends Biochim Sci 29:618–625
88
Giampiero Mei et al.