Molecular cloning and purification of Ac-TMP, a developmentally regulated putative tissue inhibitor of metalloprotease released in relative abundance by adult Ancylostoma hookworms

Am J Trop Med Hyg. 2002 Mar;66(3):238-44. doi: 10.4269/ajtmh.2002.66.238.

Abstract

A cDNA encoding a putative tissue inhibitor of metalloprotease was cloned from an Ancylostoma caninum adult hookworm cDNA library by immunoscreening with anti-hookworm secretory products antiserum. Ac-TMP (A. caninum tissue inhibitor of metalloproteinase) is encoded by a 480-bp mRNA with a predicted open reading frame of 140 amino acids (molecular weight, 16,100 Da) that contains one potential N-linked glycosylation site and an N-terminal Cys-X-Cys consensus sequence. The open reading frame corresponds to a putative hookworm tissue inhibitor of metalloproteases (TIMP) with 33% identity and 50% similarity to the N-terminal domain of human TIMP-2. Analysis by reverse transcriptase-polymerase chain reaction indicates that transcription of Ac-tmp is restricted to the adult stage. The protein was isolated from A. caninum adult secretory products by reverse-phase high-performance liquid chromatography and identified as one of the most abundant proteins released by the parasite. To our knowledge, this is the first description of a TIMP from a parasitic invertebrate.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Ancylostoma / genetics
  • Ancylostoma / metabolism*
  • Animals
  • Base Sequence
  • Chromatography, High Pressure Liquid
  • Cloning, Molecular*
  • DNA, Complementary / genetics
  • Electrophoresis, Polyacrylamide Gel
  • Gene Expression Regulation, Developmental
  • Molecular Sequence Data
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Tissue Inhibitor of Metalloproteinases / chemistry
  • Tissue Inhibitor of Metalloproteinases / genetics*
  • Tissue Inhibitor of Metalloproteinases / isolation & purification
  • Tissue Inhibitor of Metalloproteinases / metabolism

Substances

  • DNA, Complementary
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinases