title: alpha 2-Macroglobulin is cleaved by HIV-1 protease in the bait region but not in the C-terminal inter-domain region.
abstract: alpha 2-Macroglobulin is cleaved by human immunodeficiency virus-1 protease. The cleavage site is the Phe684-Tyr685 bond in the "bait region", an exposed part of alpha 2-macroglobulin, creating the "F-form". The methylamine derivative of alpha 2-macroglobulin is also cleaved at the same bond. The homologous chicken ovomacroglobulin does not form an F-form structure with the protease, although, F-form generation by other enzymes is known. This is possibly due to the lack of a suitable cleavage sequence in the corresponding region of ovomacroglobulin. In human alpha 2-macroglobulin, the interdomain segment between the main part of the molecule and the receptor-binding C-terminal domain is not cleaved by the HIV protease although typical cleavage sequences occur. In AIDS, therefore, HIV protease from infected cells in unlikely to interfere with receptor-binding of alpha 2-macroglobulin.
authors.affiliation: Max-Planck-Institut für Biochemie, Martinsried bei München.
authors.forename: U C
authors.initials: UC
authors.lastname: Meier
authors.forename: A
authors.initials: A
authors.lastname: Billich
authors.forename: K
authors.initials: K
authors.lastname: Mann
authors.forename: H J
authors.initials: HJ
authors.lastname: Schramm
authors.forename: W
authors.initials: W
authors.lastname: Schramm
mesh_terms: D000595:Amino Acid Sequence / Q000187:drug effects; D000818:Animals; D002645:Chickens; D016333:HIV Protease / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D008259:Macroglobulins / Q000737:chemistry / Q000187:drug effects; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation / Q000187:drug effects; D013329:Structure-Activity Relationship; D000511:alpha-Macroglobulins / Q000737:chemistry* / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D008259:Macroglobulins; D000511:alpha-Macroglobulins; C036828:ovomacroglobulin; D016333:HIV Protease