Abstract
The causative agents of malaria have developed a sophisticated machinery for entering multiple cell types in the human and insect hosts. In this machinery, a critical interaction occurs between the unusual myosin motor MyoA and the MyoA-tail Interacting Protein (MTIP). Here we present one crystal structure that shows three different conformations of Plasmodium MTIP, one of these in complex with the MyoA-tail, which reveal major conformational changes in the C-terminal domain of MTIP upon binding the MyoA-tail helix, thereby creating several hydrophobic pockets in MTIP that are the recipients of key hydrophobic side chains of MyoA. Because we also show that the MyoA helix is able to block parasite growth, this provides avenues for designing antimalarials.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4852-4857 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 103 |
| Issue number | 13 |
| DOIs | |
| State | Published - Mar 28 2006 |
| Externally published | Yes |
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Keywords
- Cell invasion machinery
- Gliding motility
- Myosin-tail-interacting protein
- Plasmodium
ASJC Scopus subject areas
- Genetics
- General
Cite this
Structure of the MTIP-MyoA complex, a key component of the malaria parasite invasion motor. / Bosch, Jürgen; Turley, Stewart; Daly, Thomas M.; Bogh, Stephen M.; Villasmil, Michelle L.; Roach, Claudia; Zhou, Na; Morrisey, Joanne M.; Vaidya, Akhil B.; Bergman, Lawrence W.; Hol, Wim G J.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 13, 28.03.2006, p. 4852-4857.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Structure of the MTIP-MyoA complex, a key component of the malaria parasite invasion motor
AU - Bosch, Jürgen
AU - Turley, Stewart
AU - Daly, Thomas M.
AU - Bogh, Stephen M.
AU - Villasmil, Michelle L.
AU - Roach, Claudia
AU - Zhou, Na
AU - Morrisey, Joanne M.
AU - Vaidya, Akhil B.
AU - Bergman, Lawrence W.
AU - Hol, Wim G J
PY - 2006/3/28
Y1 - 2006/3/28
N2 - The causative agents of malaria have developed a sophisticated machinery for entering multiple cell types in the human and insect hosts. In this machinery, a critical interaction occurs between the unusual myosin motor MyoA and the MyoA-tail Interacting Protein (MTIP). Here we present one crystal structure that shows three different conformations of Plasmodium MTIP, one of these in complex with the MyoA-tail, which reveal major conformational changes in the C-terminal domain of MTIP upon binding the MyoA-tail helix, thereby creating several hydrophobic pockets in MTIP that are the recipients of key hydrophobic side chains of MyoA. Because we also show that the MyoA helix is able to block parasite growth, this provides avenues for designing antimalarials.
AB - The causative agents of malaria have developed a sophisticated machinery for entering multiple cell types in the human and insect hosts. In this machinery, a critical interaction occurs between the unusual myosin motor MyoA and the MyoA-tail Interacting Protein (MTIP). Here we present one crystal structure that shows three different conformations of Plasmodium MTIP, one of these in complex with the MyoA-tail, which reveal major conformational changes in the C-terminal domain of MTIP upon binding the MyoA-tail helix, thereby creating several hydrophobic pockets in MTIP that are the recipients of key hydrophobic side chains of MyoA. Because we also show that the MyoA helix is able to block parasite growth, this provides avenues for designing antimalarials.
KW - Cell invasion machinery
KW - Gliding motility
KW - Myosin-tail-interacting protein
KW - Plasmodium
UR - http://www.scopus.com/inward/record.url?scp=33645531531&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645531531&partnerID=8YFLogxK
U2 - 10.1073/pnas.0510907103
DO - 10.1073/pnas.0510907103
M3 - Article
VL - 103
SP - 4852
EP - 4857
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 13
ER -