The Next Generation in Membrane Protein Structure Determination

187 Pages·2016·6.814 MB·English

by  Isabel Moraes (eds.)

Advances in Experimental Medicine and Biology 922
Isabel Moraes Editor
The Next
Generation
in Membrane
Protein Structure
Determination
Advances in Experimental Medicine
and Biology
Volume 922
EditorialBoard
IRUNR.COHEN,TheWeizmannInstituteofScience,Rehovot,Israel
N.S.ABELLAJTHA,KlineInstituteforPsychiatricResearch,Orangeburg,
NY,USA
JOHND.LAMBRIS,UniversityofPennsylvania,Philadelphia,PA,USA
RODOLFOPAOLETTI,UniversityofMilan,Milan,Italy
Moreinformationaboutthisseriesathttp://www.springer.com/series/5584
Isabel Moraes
Editor
The Next Generation
in Membrane Protein
Structure Determination
123
Editor
IsabelMoraes
MembraneProteinLaboratory
DiamondLightSource/ImperialCollegeLondon
HarwellCampus
Didcot,Oxfordshire,UK
ISSN0065-2598 ISSN2214-8019 (electronic)
AdvancesinExperimentalMedicineandBiology
ISBN978-3-319-35070-7 ISBN978-3-319-35072-1 (eBook)
DOI10.1007/978-3-319-35072-1
LibraryofCongressControlNumber:2016950435
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Preface
Over the years membrane proteins have fascinated scientists for playing
a fundamental role in many critical biological processes. Located across
the native cell membrane or mitochondria wall, integral membrane proteins
perform a large diversity of vital functions including energy production,
transport of ions and/or molecules across the membrane and signaling.
Mutations or improper folding of these proteins are associated with many
knowndiseasessuchasAlzheimer’s,Parkinson’s,depression,heartdisease,
cysticfibrosis,obesity,cancerandmanyothers.Itisestimatedthatmorethan
onequarterofthehumangenomecodesforintegralmembraneproteinsand
it is therefore imperative to investigate the role of these proteins in human
health and diseases. Today, around 60% of the drugs on the market target
membraneproteins.Althoughmostofthecommerciallyavailabledrugshave
beenfacilitatedbyconventionaldrugdiscoverymethods,itistheinformation
provided by the protein atomic structures that discloses details regarding
the binding mode of drugs. In addition, atomic structures contribute to a
better understanding of the protein function, mechanism, and regulation at
the molecular level. Consequently, membrane protein structural information
playsasignificantrolenotjustinmedicinebutalsoinmanypharmaceutical
drugdiscoveryprograms.
More than 30 years have passed since the first atomic structure of an in-
tegralmembraneproteinwassolved(Deisenhoferetal.1985).Nevertheless,
the number of membrane protein structures available, when compared with
solubleproteinsisstillverylow(http://blanco.biomol.uci.edu/mpstruc/)and
the main reason for this has been the many technical challenges associated
withproteinexpression,purification,andthegrowthofwell-orderedcrystals
for X-ray structure determination. In the last few years, developments
in recombinant methods for overexpression of membrane proteins; new
detergents/lipids for more efficient extraction and solubilisation; protein
engineering through mutations, deletions, fusion partners and monoclonal
antibodiestopromotediffractionqualitycrystals;automation/miniaturization
andsynchrotron/beamlinedevelopmentshavebeencrucialtorecentsuccesses
inthefield.Inaddition,developmentsincomputationalapproacheshavebeen
ofextremelyvaluableimportancetothelinkbetweentheproteinstructureand
its physiological function. Molecular dynamics simulations combined with
homologymodelinghasbecomeapowerfultoolinthedevelopmentofnovel
pharmacologicaldrugtargets.
v
vi Preface
Thechapterspresentedinthisbookprovideauniquecoverageofdifferent
methods and developments essential to the field of membrane proteins
structural biology. The contributor authors are all experts in their respective
fieldsanditisourhopethatthematerialfoundwithinthebookwillprovide
valuableinformationtoalltheresearcherswhetherexpertsornew.
Oxfordshire,UK IsabelMoraes
February2016
Acknowledgments
Theeditorwishtothanktoalltheauthorswhoenthusiasticallyhaveagreed
to be part of this volume. The research of the editor is supported by the
Wellcome Trust grant 099165/Z/12/Z and by the EU Marie Curie FP7-
PEOPLE-2011-ITNNanoMem.
vii

Contents
1 Expression Screening of Integral Membrane Proteins
byFusiontoFluorescentReporters........................ 1
Louise E. Bird, Joanne E. Nettleship, Valtteri Järvinen,
HeatherRada,AnilVerma,andRaymondJ.Owens
2 Detergents in Membrane Protein Purification
andCrystallisation...................................... 13
AnandhiAnandanandAliceVrielink
3 NMRofMembraneProteins:BeyondCrystals.............. 29
SundaresanRajesh,MichaelOverduin,andBoyanB.Bonev
4 CharacterisationofConformationalandLigandBinding
Properties of Membrane Proteins Using Synchrotron
RadiationCircularDichroism(SRCD)..................... 43
RohanahHussainandGiulianoSiligardi
5 Membrane Protein Crystallisation: Current Trends
andFuturePerspectives.................................. 61
JoanneL.ParkerandSimonNewstead
6 CrystalDehydrationinMembraneProtein
Crystallography......................................... 73
JuanSanchez-WeatherbyandIsabelMoraes
7 NonlinearOpticalCharacterizationofMembraneProtein
MicrocrystalsandNanocrystals........................... 91
JustinA.NewmanandGarthJ.Simpson
8 ExploitingMicrobeamsforMembraneProteinStructure
Determination.......................................... 105
Anna J. Warren, Danny Axford, Neil G. Paterson,
andRobinL.Owen
9 ApplicationsoftheBLENDSoftwaretoCrystallographic
DatafromMembraneProteins............................ 119
PierreAller,TianGeng,GwyndafEvans,andJamesFoadi
10 SerialMillisecondCrystallographyofMembraneProteins... 137
Kathrin Jaeger, Florian Dworkowski, Przemyslaw Nogly,
ChristopherMilne,MeitianWang,andJoergStandfuss
ix