The structure of the D3 domain of Plasmodium falciparum myosin tail interacting protein MTIP in complex with a nanobody.

TitleThe structure of the D3 domain of Plasmodium falciparum myosin tail interacting protein MTIP in complex with a nanobody.
Publication TypeJournal Article
Year of Publication2013
AuthorsKhamrui, S., S. Turley, E. Pardon, J. Steyaert, E. Fan, C. L. M. J. Verlinde, L. W. Bergman, and W. G. J. Hol
JournalMol Biochem Parasitol
Volume190
Issue2
Pagination87-91
Date Published2013 Aug
ISSN1872-9428
Abstract

Apicomplexan parasites enter host cells by many sophisticated steps including use of an ATP-powered invasion machinery. The machinery consists of multiple proteins, including a special myosin (MyoA) which moves along an actin fiber and which is connected to the myosin tail interaction protein (MTIP). Here we report a crystal structure of the major MyoA-binding domain (D3) of Plasmodium falciparum MTIP in complex with an anti-MTIP nanobody. In this complex, the MyoA-binding groove in MTIP-D3 is considerably less accessible than when occupied by the MyoA helix, due to a shift of two helices. The nanobody binds to an area slightly overlapping with the MyoA binding groove, covering a hydrophobic region next to the groove entrance. This provides a new avenue for arriving at compounds interfering with the invasion machinery since small molecules binding simultaneously to the nanobody binding site and the adjacent MyoA binding groove would prevent MyoA binding by MTIP.

DOI10.1016/j.molbiopara.2013.06.003
Alternate JournalMol. Biochem. Parasitol.
PubMed ID23831371
Grant ListAI48226 / AI / NIAID NIH HHS / United States
R01 AI048226 / AI / NIAID NIH HHS / United States