receptor revealed by HDX. Structure
19:1424–1432
21. Chung KY, Rasmussen SGF, Liu T et al (2011)
Conformational changes in the G protein Gs
induced by the β2 adrenergic receptor. Nature
477:611–615
22. Zhang X, Chien EYT, Chalmers MJ et al
(2010) Dynamics of the beta2-adrenergic
G-protein coupled receptor revealed by
hydrogen-deuterium exchange. Anal Chem
82:1100–1108
23. Mouchlis VD, Chen Y, McCammon JA et al
(2018) Membrane allostery and unique hydrophobic sites promote enzyme substrate specificity. J Am Chem Soc 140:3285–3291
24. Siempelkamp BD, Rathinaswamy MK, Jenkins
ML et al (2017) Molecular mechanism of activation of class IA phosphoinositide 3-kinases
(PI3Ks) by membrane-localized HRas. J Biol
Chem 292:12256–12266
25. Dornan GL, Siempelkamp BD, Jenkins ML
et al (2017) Conformational disruption of
PI3Kδ regulation by immunodeficiency mutations in PIK3CD and PIK3R1. Proc Natl Acad
Sci USA 114:1982–1987
26. Masson GR, Perisic O, Burke JE et al (2016)
The intrinsically disordered tails of PTEN and
PTEN-L have distinct roles in regulating substrate specificity and membrane activity. Biochem J 473:135–144
27. Vadas O, Dbouk HA, Shymanets A et al (2013)
Molecular determinants of PI3Kγ-mediated
activation downstream of G-protein-coupled
receptors (GPCRs). Proc Natl Acad Sci U S A
110:18862–18867
28. Cao J, Burke JE, Dennis EA (2013) Using
hydrogen/deuterium exchange mass spectrometry to define the specific interactions of
the phospholipase A2 superfamily with lipid
substrates, inhibitors, and membranes. J Biol
Chem 288:1806–1813
29. Dbouk HA, Vadas O, Shymanets A et al (2012)
G protein-coupled receptor-mediated activation of p110β by Gβγ is required for cellular
transformation and invasiveness. Sci Signal 5:
ra89–ra89
30. Burke JE, Perisic O, Masson GR et al (2012)
Oncogenic mutations mimic and enhance
dynamic events in the natural activation of
phosphoinositide 3-kinase p110α (PIK3CA).
Proc Natl Acad Sci U S A 109:15259–15264
31. Burke JE, Vadas O, Berndt A et al (2011)
Dynamics of the phosphoinositide 3-kinase
p110δ interaction with p85α and membranes
reveals aspects of regulation distinct from
p110α. Structure 1993(19):1127–1137
32. Hsu Y-H, Burke JE, Li S et al (2009) Localizing the membrane binding region of Group
VIA Ca2+Àindependent phospholipase A2
using peptide amide hydrogen/deuterium
exchange mass spectrometry. J Biol Chem
284:23652–23661
33. Burke JE, Hsu Y-H, Deems RA et al (2008) A
phospholipid substrate molecule residing in the
membrane surface mediates opening of the lid
region in group IVA cytosolic phospholipase
A2. J Biochem 283:31227–31236
34. Burke JE, Karbarz MJ, Deems RA et al (2008)
Interaction of group IA phospholipase A2 with
metal ions and phospholipid vesicles probed
with deuterium exchange mass spectrometry.
Biochemistry 47:6451–6459
35. Hamuro Y (2017) Determination of equine
cytochrome c backbone amide hydrogen/deuterium exchange rates by mass spectrometry
using a wider time window and isotope envelope. J Am Soc Mass Spectrom 28:486–497
36. Guttman M, Weis DD, Engen JR et al (2013)
Analysis of overlapped and noisy hydrogen/
deuterium exchange mass spectra. J Am Soc
Mass Spectrom 24:1906–1912
37. Weis DD, Wales TE, Engen JR et al (2006)
Identification and characterization of EX1
kinetics in H/D exchange mass spectrometry
by peak width analysis. J Am Soc Mass Spectrom 17:1498–1509
38. Engen JR, Wales TE (2015) Analytical aspects
of hydrogen exchange mass spectrometry.
Annu Rev Anal Chem 8:127–148
39. Wales TE, Eggertson MJ, Engen JR (2013)
Considerations in the analysis of hydrogen
exchange mass spectrometry data. Methods
Mol Biol 1007:263–288
40. Yan X, Zhang H, Watson J et al (2002) Hydrogen/deuterium exchange and mass spectrometric analysis of a protein containing
multiple disulfide bonds: Solution structure of
recombinant macrophage colony stimulating
factor-beta (rhM-CSFbeta). Protein Sci
11:2113–2124
41. Connelly GP, Bai Y, Jeng MF et al (1993)
Isotope effects in peptide group hydrogen
exchange. Proteins 17:87–92
42. Walters BT, Ricciuti A, Mayne L et al (2012)
Minimizing back exchange in the hydrogen
exchange-mass spectrometry experiment. J
Am Soc Mass Spectrom 23:2132–2139
43. Ahn J, Jung MC, Wyndham K et al (2012)
Pepsin immobilized on high-strength hybrid
particles for continuous flow online digestion
at 10,000 psi. Anal Chem 84:7256–7262
44. Lin K, Lin J, Wu W-I et al (2012) An ATP-site
on-off switch that restricts phosphatase accessibility of Akt. Sci Signal 5:ra37–ra37
Probing Protein-Membrane Interactions Using HDX-MS
485
19:1424–1432
21. Chung KY, Rasmussen SGF, Liu T et al (2011)
Conformational changes in the G protein Gs
induced by the β2 adrenergic receptor. Nature
477:611–615
22. Zhang X, Chien EYT, Chalmers MJ et al
(2010) Dynamics of the beta2-adrenergic
G-protein coupled receptor revealed by
hydrogen-deuterium exchange. Anal Chem
82:1100–1108
23. Mouchlis VD, Chen Y, McCammon JA et al
(2018) Membrane allostery and unique hydrophobic sites promote enzyme substrate specificity. J Am Chem Soc 140:3285–3291
24. Siempelkamp BD, Rathinaswamy MK, Jenkins
ML et al (2017) Molecular mechanism of activation of class IA phosphoinositide 3-kinases
(PI3Ks) by membrane-localized HRas. J Biol
Chem 292:12256–12266
25. Dornan GL, Siempelkamp BD, Jenkins ML
et al (2017) Conformational disruption of
PI3Kδ regulation by immunodeficiency mutations in PIK3CD and PIK3R1. Proc Natl Acad
Sci USA 114:1982–1987
26. Masson GR, Perisic O, Burke JE et al (2016)
The intrinsically disordered tails of PTEN and
PTEN-L have distinct roles in regulating substrate specificity and membrane activity. Biochem J 473:135–144
27. Vadas O, Dbouk HA, Shymanets A et al (2013)
Molecular determinants of PI3Kγ-mediated
activation downstream of G-protein-coupled
receptors (GPCRs). Proc Natl Acad Sci U S A
110:18862–18867
28. Cao J, Burke JE, Dennis EA (2013) Using
hydrogen/deuterium exchange mass spectrometry to define the specific interactions of
the phospholipase A2 superfamily with lipid
substrates, inhibitors, and membranes. J Biol
Chem 288:1806–1813
29. Dbouk HA, Vadas O, Shymanets A et al (2012)
G protein-coupled receptor-mediated activation of p110β by Gβγ is required for cellular
transformation and invasiveness. Sci Signal 5:
ra89–ra89
30. Burke JE, Perisic O, Masson GR et al (2012)
Oncogenic mutations mimic and enhance
dynamic events in the natural activation of
phosphoinositide 3-kinase p110α (PIK3CA).
Proc Natl Acad Sci U S A 109:15259–15264
31. Burke JE, Vadas O, Berndt A et al (2011)
Dynamics of the phosphoinositide 3-kinase
p110δ interaction with p85α and membranes
reveals aspects of regulation distinct from
p110α. Structure 1993(19):1127–1137
32. Hsu Y-H, Burke JE, Li S et al (2009) Localizing the membrane binding region of Group
VIA Ca2+Àindependent phospholipase A2
using peptide amide hydrogen/deuterium
exchange mass spectrometry. J Biol Chem
284:23652–23661
33. Burke JE, Hsu Y-H, Deems RA et al (2008) A
phospholipid substrate molecule residing in the
membrane surface mediates opening of the lid
region in group IVA cytosolic phospholipase
A2. J Biochem 283:31227–31236
34. Burke JE, Karbarz MJ, Deems RA et al (2008)
Interaction of group IA phospholipase A2 with
metal ions and phospholipid vesicles probed
with deuterium exchange mass spectrometry.
Biochemistry 47:6451–6459
35. Hamuro Y (2017) Determination of equine
cytochrome c backbone amide hydrogen/deuterium exchange rates by mass spectrometry
using a wider time window and isotope envelope. J Am Soc Mass Spectrom 28:486–497
36. Guttman M, Weis DD, Engen JR et al (2013)
Analysis of overlapped and noisy hydrogen/
deuterium exchange mass spectra. J Am Soc
Mass Spectrom 24:1906–1912
37. Weis DD, Wales TE, Engen JR et al (2006)
Identification and characterization of EX1
kinetics in H/D exchange mass spectrometry
by peak width analysis. J Am Soc Mass Spectrom 17:1498–1509
38. Engen JR, Wales TE (2015) Analytical aspects
of hydrogen exchange mass spectrometry.
Annu Rev Anal Chem 8:127–148
39. Wales TE, Eggertson MJ, Engen JR (2013)
Considerations in the analysis of hydrogen
exchange mass spectrometry data. Methods
Mol Biol 1007:263–288
40. Yan X, Zhang H, Watson J et al (2002) Hydrogen/deuterium exchange and mass spectrometric analysis of a protein containing
multiple disulfide bonds: Solution structure of
recombinant macrophage colony stimulating
factor-beta (rhM-CSFbeta). Protein Sci
11:2113–2124
41. Connelly GP, Bai Y, Jeng MF et al (1993)
Isotope effects in peptide group hydrogen
exchange. Proteins 17:87–92
42. Walters BT, Ricciuti A, Mayne L et al (2012)
Minimizing back exchange in the hydrogen
exchange-mass spectrometry experiment. J
Am Soc Mass Spectrom 23:2132–2139
43. Ahn J, Jung MC, Wyndham K et al (2012)
Pepsin immobilized on high-strength hybrid
particles for continuous flow online digestion
at 10,000 psi. Anal Chem 84:7256–7262
44. Lin K, Lin J, Wu W-I et al (2012) An ATP-site
on-off switch that restricts phosphatase accessibility of Akt. Sci Signal 5:ra37–ra37
Probing Protein-Membrane Interactions Using HDX-MS
485