Animal Lectins: Form, Function and Clinical Applications PDF
Preview Animal Lectins: Form, Function and Clinical Applications
Animal Lectins: Form, Function and Clinical Applications . G.S. Gupta Animal Lectins: Form, Function and Clinical Applications In Collaboration with Anita Gupta and Rajesh K. Gupta Principalauthor G.S.Gupta,Ph.D. PanjabUniversity Chandigarh160014 India ISBN978-3-7091-1064-5 ISBN978-3-7091-1065-2(eBook) DOI10.1007/978-3-7091-1065-2 SpringerWienHeidelbergNewYorkDordrechtLondon LibraryofCongressControlNumber:2012945422 #Springer-VerlagWien2012 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpartofthematerialis concerned,specificallytherightsoftranslation,reprinting,reuseofillustrations,recitation,broadcasting,reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. 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Thepublishermakesnowarranty,expressorimplied,withrespecttothematerialcontainedherein. Printedonacid-freepaper SpringerispartofSpringerScience+BusinessMedia(www.springer.com) Foreword I Lectinsaretypicallycarbohydrate-bindingproteinsthatarewidelydistributedinNature.With thegrowinginterestinthefieldofglycobiology,thebodyofresearchrelatedtoanimallectins has grown at an explosive rate, particularly in the past 25 years. However, the Lectinology fieldisstillrelativelyyoung,nascent,andevolving.“AnimalLectins:Form,Functionand ClinicalApplications”presentsthemostup-to-dateanalysisofthesecarbohydrate-binding, andpotentiallylifesavingproteinsintwocomprehensivevolumes.Lectionologyisanexciting areaofresearchthathashelpedimmenselyinourunderstandingofhost-pathogeninteractions. Importantly,C-typelectinscanactaspattern-recognitionreceptors(PRR)thatsenseinvading pathogens. The interactions between lectins and carbohydrates have been shown to be involved in diverse activities such as opsonizationof microbes, cell adhesion andmigration,cellactiva- tionanddifferentiation,andapoptosis.Developmentsintheareaoflectinresearchhasopened anewaspectinstudyingtheimmunesystem,andatthesametime,providednewtherapeutic routesforthetreatmentandpreventionofdiseases. Thispresentbookonanimallectinsdiscussesthebiochemicalandbiophysicalpropertiesof animal lectins at length along with their functions in health and diseases. Importantly, the potentialinterrelationshipsbetweenlectinsoftheinnateimmunesystemandlatentvirusesthat reside within host cells, sometimes integrated into the genome have been beautifully highlighted. These interactions help to explain autoimmune diseases and shed light on the developmentofcancerdiagnostics.Thepresentbookonanimallectinspresentsnewinsights intothebiologicalrolesofmostanimallectins,includingtheirroleinpreventionofinfections through innate immunity. The contents of “Animal Lectins: Form, Function and Clinical Applications”providefunctionalexplanationfortheenormousdiversityofglycanstructures foundonanimalcells.Therearestillseveralotherareaswhereinlectinsandtheirspecificities are not well defined and the biological functions of the interactions remain elusive, thereby underscoring the need for further research. The book offers novel ideas for students of Immunology, Microbiology, as well as young researchers in the area of Biochemistry. Icongratulatetheauthorsincompletingthistrulyenormoustask. Prof.N.K.Ganguly,MD,DSc(hc),FMedSci(London), FRCPath(London),FAMS,FNA,FASc,FNASc, FTWAS(Italy),FIACS(Canada),FIMSA President,JIPMER FormerDirectorGeneral,ICMR Pondicherry,India FormerDirector,PGIMER,Chandigarh v . Foreword II Lectins are proteinsthatbind tosoluble carbohydratesaswell astothefunctionalgroups of carbohydratechainsthatarepartofaglycoproteinorglycolipidfoundonthesurfacesofcells. Lectinsareknowntobewidespreadinnatureandplayaroleininteractionsandcommunica- tionbetweencellstypicallyforrecognition.Carbohydratesonthesurfaceofonecellbindto the binding sites of lectins on the surface of another cell. For example, some bacteria use lectinstoattachthemselvestothecellsofthehostorganismduringinfection.Bindingresults from numerous weak interactions which come together to form a strong attraction. A lectin usually contains two or more binding sites for carbohydrate units. In addition, the carbohydrate-binding specificityofacertainlectin is determinedby the amino acidresidues that bind to the carbohydrates. Most of the lectins are essentially nonenzymic in action and nonimmune in origin. They typically agglutinate certain animal cells and/or precipitate glycoconjugates. Plant lectins are highly resistant to breakdown from heat or digestion. Theyprovideadefenseforplantsagainstbacteria,viruses,andotherinvaders,butcancreate problemsforhumans.Inanimals,lectinsregulatethecelladhesiontoglycoproteinsynthesis, controlproteinlevelsinblood,andbindsolubleextracellularandintracellularglycoproteins. Also,intheimmunesystem,lectinsrecognizecarbohydratesfoundspecificallyonpathogens orthosethatarenotrecognizableonhostcells.Embryosareattachedtotheendometriumof theuterusthroughL-selectin.Thisactivatesasignaltoallowforimplantation.E.coliareable toresideinthegastrointestinaltractbylectinsthatrecognizecarbohydratesintheintestines. The influenza virus contains hemagglutinin, which recognizes sialic acid residues on the glycoproteinslocatedonthesurfaceofthehostcell.Thisallowsthevirustoattachandgain entry into the host cell. Clinically, purified lectins can be used to identify glycolipids and glycoproteinsonanindividual’sredbloodcellsforbloodtyping. ThejourneyofAnimalLectins:Form,Function,andClinicalApplications,essentiallythe Encyclopedia of Animal Lectins, starts with an introductory chapter on lectin families, in general, followed by specific animal lectin families, such as intracellular sugar-binding ER chaperones,calnexinandcalreticulin;theP-typelectinsworkingintheendocyticpathway,the lectins of ERAD pathway, and the complex mannose-binding ERGIC-53 protein and its orthologs circulating between the ER, ERGIC, and the Golgi apparatus; and the fairly small galectinsthataresynthesizedinthecytosolbutmaybefoundatmanylocations.Chapterson R-type lectin families, pentraxins, siglecs, C-type lectins, regenerating gene family, tetranectin group of lectins, ficolins, F-type lectins, and chi-lectins have covered the up-to- dateliteratureonthesubjectandcontainillustrationsoftheirstructures,functions,andclinical applications.Theemerginggroupofannexinsaslectinshasbeengivenaplaceasaseparate family. The C-type lectins comprising 17 subfamilies such as collectins, selectins, NK cell lectin receptors, latest discoveries of lectins on dendritic cells and others form the backbone of Volume2.Thechaptersarewellwritten,althoughthereisvariabilityonhowtheyarefocused. Most of the chapters focus on lectin structures, functions, their ligands, and their medical vii viii ForewordII relevance in terms of diagnosis and therapy. The journey ends with five reviews on clinical applications of lectins with a survey of literature on endogenous lectins asdrug targets.This mayreflectstateoftheartineachareaortheinterestsoftheauthor(s). Inpost-genomicyears,withthehumangenomesequenceathand,acompleteoverviewof many human lectin genes has become available, as illustrated by C-type lectin domain 3D structureshavingaslittleas30%aminoacidsequencesimilarity.Themajoreffortinthefuture will be on elaboration of similar studies on other families of lectins with carbohydrate specificitiesandinvivolectin–ligandinteractions.Inthisrespect,furtherwritingswillbring thereadertotheforefrontofknowledgeinthefield.Thus,onthirstoflearningaboutanimal recognitionsystems,AnimalLectins:Form,Function,andClinicalApplicationsisanexcel- lent reference book for those studying biochemistry, biotechnology, and biophysics with a specialization in the areas of immunology, lectinology, and glycobiology as well as for pharmacy students involved in drug discoveries through lectin–carbohydrate interactions. Both novice and advanced researchers in biomedical, analytical, and pharmaceutical fields needtounderstandanimallectins. T.P.Singh,F.N.A.,F.A.Sc.,F.N.A.Sc.,F.T.W.A.S DBT-DistinguishedBiotechnologyResearchProfessor DepartmentofBiophysics, AllIndiaInstituteofMedicalSciences,NewDelhi,India Preface Lectins are phylogenetically ancient proteins that have specific recognition and binding functions for complex carbohydrates of glycoconjugates, that is, of glycoproteins, proteoglycans/glycosaminoglycans, and glycolipids. They occur ubiquitously in nature and typicallyagglutinatecertainanimalcellsand/orprecipitateglycoconjugateswithoutaffecting theircovalentlinkages.Lectinsmediateavarietyofbiologicalprocesses,suchascell–celland host–pathogen interactions, serum–glycoprotein turnover, and innate immune responses. Although originally isolated from plant seeds, they are now known to be ubiquitously distributedinnature.Thesuccessfulcompletionofseveralgenomeprojectshasmadeamino acidsequencesofseverallectinsavailable.Theirtertiarystructuresprovideagoodframework upon which all other data can be integrated, enabling the pursuit of the ultimate goal of understanding these molecules at the atomic level. With growing interest in the field of glycobiology,thefunction–structurerelationsofanimallectinshaveincreasedatanexplosive rate, particularly in the last 20 years. Since lectins mediate important processes of adhesion and communication both inside and outside the cells in association with their ligands and associatedco-receptorproteins,thereisaneedofareferencebookthatcandescribeemerging applicationsontheprinciplesofstructuralbiologyofanimallectinsatonepoint.Nobookhas ever described in a coordinated fashion structures, functions, and clinical applications of 15 families of animal lectins presently known. Therefore, with the increasing information on animallectinsinbiomedicalresearchandtheirtherapeuticapplications,writingofacompre- hensive document on animal lectins and associated proteins in the form of Animal Lectins: Form, Function, and ClinicalApplications has been the main objective ofthe present work. The entire manuscript has been distributed into two volumes in order to produce an easily readable work with easy portability. Volume 1 comprises most of the superfamilies (Chaps. 1–21)oflectins,excludingC-typelectinsorC-type-lectin-likedomain.Involume2,wehave mainly focused on C-type lectins, which have been extensively studied in vertebrates with widerclinicalapplications(Chaps.22–46). AnimalLectins:Form,Function,andClinicalApplicationsreviewsthecurrentknowledge of animal lectins, their ligands, and associated proteins with a focus on their structures and functions, biochemistry and patho-biochemistry (protein defects as a result of disease), cell biology(exocytosisandendocytosis,apoptosis,celladhesion,andmalignanttransformation), clinicalapplications,andtheirinterventionfortherapeuticpurposes.Thebookemphasizeson theeffectorfunctionsofanimallectinsininnateimmunityandprovidesreviews/chapterson extracellularanimallectins,suchasC-typelectins,R-typelectins,siglecs,andgalectins,and intracellularlectins,suchascalnexinfamily(M-type,L-type,andP-type),recentlydiscovered F-box lectins, ficolins, chitinase-like lectins, F-type lectins, and intelectins, mainly in vertebrates. The clinical significance of lectin–glycoconjugate interactions has been exemplified by inflammatorydiseases,defectsof immune defense, autoimmunity,infectious diseases, and tumorigenesis/metastasis, along with therapeutic perspectives of novel drugs thatinterferewithlectin–carbohydrateinteractions. Basedontheinformationgatheredonanimallectinsinthisbook,avarietyofmedicaland other applications are in the offing. Foremost among these is the lectin-replacement therapy forpatientssufferingfromlectindeficiencydefects.Wehavepointedouttheadvancementsof ix x Preface suchstudieswheresuchprogresshasbeenmade.Otherusesindifferentstagesofdevelopment are antibacterial drugs; multivalent hydrophobic carbohydrates for anti-adhesion therapy of microbial diseases; highly effective inhibitors of the selectins for treatment of leucocyte- mediatedpathogenicconditions,suchasasthma,septicshock,stroke,andmyocardialinfarc- tion; inhibitors of the galectins and other lectins involved in metastasis; and application of lectinsforfacileandimproveddiseasediagnosis.RecentadvancesinthediscoveryofM6PR- homologousproteinfamily(Chap.5),lectinsofERADpathway,F-boxproteinsandM-type lectins (Chap. 6), and mannose receptor–targeted drugs and vaccines (Chaps. 8 and 46) can formthebasisofcutting-edgetechnologyindrugdeliverydevices. Based on the structures of animal lectins, classified into at least 15 superfamilies, C-type lectins and galectins are the classical major families. Galectins are known to be associated withcarcinogenesisandmetastasis.Galectin-3isapleiotropiccarbohydrate-bindingprotein, involved in a variety of normal and pathological biological processes. Its carbohydrate- binding properties constitute the basis for cell–cell and cell–matrix interactions (Chap. 12) andcancerprogression(Chap.13).Studiesleadtotherecognitionofgalectin-3asadiagnos- tic/prognosticmarkerforspecificcancertypes,suchasthyroidandprostate.Ininterferingwith galectin–carbohydrateinteractionsduringtumorprogression,acurrentchallengeisthedesign of specific galectin inhibitors for therapeutic purposes. Anti-galectin agents can restrict the levelsofmigrationofseveraltypesofcancercellsandshould,therefore,beusedinassociation with cytotoxic drugs to combat metastatic cancer (Chap. 13). The properties of siglecs that makethemattractiveforcell-targetedtherapieshavebeenreviewedinChaps.16,17,and46. F-type domains are found in proteins from a range of organisms from bacteria to vertebrates, but exhibit patchy distribution across different phylogenetic taxa, suggesting that F-type lectin genes have been selectively lost even between closely related lineages, thus making it difficult to trace the ancestry of the F-type domain. The F-type domain has clearly gained functional value in fish, whereas the fate of F-type domains in higher vertebrates is not clear, rather it has become defunct. Two genes encoding three-domain F-type proteins are predicted in the genome of the opossum (Monodelphis domestica), an early-branching mammal. There is plenty of scope to discover F-type lectins in mammalian vertebrates(Chap.20).SincethereportsontheC-reactiveprotein(CRP)asacardiovascular marker (Chap. 8), novel biomarkers in cardiovascular and other inflammatory diseases have emergedinrecentyears.ThesubstantialknowledgeonCRPisnowbeingcomplementedby newmarkerssuchasYKL-40,amemberofchi-lectinsgroupofCTLD(Chap.19).TheYKL- 40 (chitinase-3-like protein 1, or human cartilage glycoprotein-39) displays a typical fold of family18glycosylhydrolasesandisexpressedandsecretedbyseveraltypesofsolidtumors, including glioblastoma, colon cancer, breast cancer, and malignant melanoma. Chitinase-3- like protein 1 was recently introduced into clinical practice; yet its application is still restricted. In volume 2, we have mainly focused on C-type lectins, which have been extensively studiedinvertebrates.AC-typelectinisatypeofcarbohydrate-bindingproteindomainthat requirescalciumforbindinginteractionsingeneral.Drickameretal.classifiedC-typelectins into seven subgroups (I to VII) based on the order of the various protein domains in each protein. This classification was subsequently updated in 2002, leading to seven additional groups (VIII to XIV). A further three subgroups (XV to XVII) were added recently. The C- typelectinssharestructuralhomologyintheirhigh-affinitycarbohydraterecognitiondomains (CRDs) and constitute a large and diverse group of extracellular proteins that have been extensively studied. Their activities have been implicated as indispensable players in carbo- hydraterecognition,suggestingtheirpossibleapplicationindiscriminationofvariouscorrel- ative microbes and developing biochemical tools. The C-type lectins, structurally characterized by a double loop composed of two highly conserved disulfide bridges located atthebasesoftheloops,arebelievedtomediatepathogenrecognitionandplayimportantroles intheinnateimmunityofbothvertebratesandinvertebrates.Alargenumberoftheseproteins
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