title: Molecular mechanism and structural basis of interactions of dipeptidyl peptidase IV with adenosine deaminase and human immunodeficiency virus type-1 transcription transactivator.
abstract: Dipeptidyl peptidase IV (DPPIV or CD26) is a multifunctional membrane glycoprotein. As an exopeptidase it regulates the activity of a series of biologically important peptides. Through its interaction with specific proteins and peptides, DPPIV is also involved in a wide range of biologically relevant processes such as cell adhesion, T cell activation and apoptosis. In this paper, we review our recent studies on the interactions of DPPIV with adenosine deaminase (ADA) and the transcription transactivator of the human immunodeficiency virus type-1 (HIV-1 Tat) as revealed by three-dimensional structure reconstructed by single particle analysis of cryo-electron microscopy (EM) and crystal structures of the human DPPIV-bovine ADA complex as well as the crystal structures of DPPIV in complex with HIV-1 Tat-derived nonapeptides. These results contribute importantly to the clarification of the molecular mechanisms of this multifunctional protein. The biological relevance of these interactions is discussed.
authors.affiliation: Institut für Biochemie und Molekularbiologie, Charité-Universitätsmedizin Berlin, Arnimallee 22, 14195 Berlin-Dahlem, Germany. hua.fan@charite.de
authors.forename: Hua
authors.initials: H
authors.lastname: Fan
authors.forename: Felista Lemnyui
authors.initials: FL
authors.lastname: Tansi
authors.forename: Wilhelm Andreas
authors.initials: WA
authors.lastname: Weihofen
authors.forename: Christoph
authors.initials: C
authors.lastname: Böttcher
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: Jacobo
authors.initials: J
authors.lastname: Martinez
authors.forename: Wolfram
authors.initials: W
authors.lastname: Saenger
authors.forename: Werner
authors.initials: W
authors.lastname: Reutter
mesh_terms: D000243:Adenosine Deaminase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017434:Protein Structure, Tertiary / Q000235:genetics; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation / Q000235:genetics; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D054322:tat Gene Products, Human Immunodeficiency Virus; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; C548482:ADA protein, human; D000243:Adenosine Deaminase