MOLECULAR-CLONING OF A GENE FROM PLASMODIUM-FALCIPARUM THAT CODES FORA PROTEIN SHARING MOTIFS FOUND IN ADHESIVE MOLECULES FROM MAMMALS ANDPLASMODIA

Adhesion of Plasmodium to host cells is an important phenomenon in par asite invasion and in malaria-associated pathology. We report here the molecular cloning of a putative adhesive molecule from P. falciparum that shares both sequence and structural similarities with a sporozoit e surface molecule from Plasmodium termed the thrombospondin-related a nonymous protein (TRAP) and, to a lesser extent, with the circumsporoz oite (CS) protein. The gene, which is present on chromosome 3 as a sin gle copy, was termed CTRP for CS protein-TRAP-related protein. The ful l-length CTRP encodes a protein containing a putative signal sequence followed by a long extracellular region of 1990 amino acids, a transme mbrane domain, and a short cytoplasmic segment. The putative extracell ular region of CTRP is defined by two separated adhesive domains. The first domain contains six 210-amino acid-long homologous repeats, the sequence of which is related to the A-type domain found in adhesive mo lecules including the cu subunits of several integrins and a number of extracellular matrix glycoproteins. The second domain contains seven repeats of 87-60 amino acids in length, which share similarities with the thrombospondin type 1 domain found in a variety of adhesive molecu les. Finally, CTRP also contains consensus motifs found in the superfa mily of haematopoietin receptors. Interstrain analysis of eight differ ent parasite isolates revealed that CTRP does not show size polymorphi sm except in repetitive regions flanking potential adhesive domains.