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Table 1 Overview over the thermodynamic and aggregation fingerprints of the IgLCs of this study. All Tm values, turbidity maxima and aggregate sizes are reported at a concentration of ca. 30 μM. The DSF experiments at pH 5 (pH 7.4) were performed at a scan rate of 2.5°C/min (1.0°C/min). Data on Tm and refolding fraction by DSC and trypsin digestibility are from [13]. The concentration dependence of the melting and aggregation temperatures was explored in the range between ca. 15 and 120 μM. *m-value fixed for all samples. **Different m-value allowed in fit. ***Only one population with intermediate s-value detected

From: Widespread amyloidogenicity potential of multiple myeloma patient-derived immunoglobulin light chains

 

P001

P004

P005

P006

P007

P013

P016

P017

P020

Dimerisation by SDS-PAGE

0.96

0.71

0.43

0.3

0.32

0.36

0.49

0.4

0.52

Dimerisation by MS

1

0.97

0.35

0.07

  

0.9

0.3

0.56

Dimerisation by AUC

1

0.94

0.55

0.1

***

***

0.72

0.15

0.91

Tm DSF (pH 5) [°C]

63.7

51.1

51.0

54.9

50.3

51.7

54.1

50.4

56.3

T (max. turb. @ pH 5) [°C]

> 90

62

71

No turb.

66

64

No turb.

65

83

Tm DSC (pH 7.4) [°C]

64.6

58.5

51.2

50.4

55.4

52.2

56.8

51.7

53.5

Tm DSF (pH 7.4) [°C]

62.6

54.2

50.9

50.6

53.8

52.6

54.7

49.4

50.4

d Tm/d log(c) (pH 7.4)

−0.33

−1.19

−1.20

0.9

−0.55

−1.10

−0.17

0.15

0.23

Tagg DSF (pH 7.4) [°C]

54.9

53.0

50.8

59.4

55.2

50.2

n/a

61.7

50.3

d Tagg/d log(c) (pH7.4)

−5.8

−2.9

−4.1

−1.5

−3.2

−4.1

−0.5

−22.0

−4.6

Cumul. rad. (pH 7.4, 70°C) [nm]

>1000

>1000

~1000

7

~300

~25

5.5

16

>1000

Fract. refold - DSF (no urea)

Small

Small

Small

Large

Small

Small

Medium

Large

Small

Fract. refold - DSF (2 M urea)

0

> 50

> 50

> 50

> 50

< 50

< 50

> 50

< 50

Fract. refold - DSC

0

0.18

0.36

0.68

0.33

0.38

0.41

0.7

0.22

ΔG [kJ/mol] at 37°C

26.3±1.5

25.3±0.4

20.8±2.1

20.8±0.8

23.7±0.6

21.2±0.7

10.0±0.7

21.8±1.1

20.2±0.5

m-value

7.1*

7.1*

7.1*

7.1*

7.1*

7.1*

2.3±0.5**

7.1*

7.1*

Digestibility by trypsin

0.1

1

0.7

0.24

1

1

0.17

0.98

1

Acid induced amyloid form

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes