4OKU

Structure of Toxoplasma gondii proMIC2

Summary for 4OKU

• Entry DOI: 10.2210/pdb4oku/pdb
• Related: 4OKR
• Descriptor: Micronemal protein MIC2, alpha-D-mannopyranose (2 entities in total)
• Functional Keywords: vwa, integrin i domain, tsr domain, adhesin, gliding motility, cell adhesion
• Biological source: Toxoplasma gondii
• Total number of polymer chains: 2
• Total formula weight: 68058.58

Authors

Song, G.,Springer, T.A. (deposition date: 2014-01-22, release date: 2014-03-19, Last modification date: 2024-10-30)

Primary citation

Song, G.,Springer, T.A.
Structures of the Toxoplasma gliding motility adhesin.
Proc.Natl.Acad.Sci.USA, 111:4862-4867, 2014

PubMed Abstract: Micronemal protein 2 (MIC2) is the key adhesin that supports gliding motility and host cell invasion by Toxoplasma gondii. With a von Willebrand factor A (VWA) domain and six thrombospondin repeat domains (TSR1-6) in its ectodomain, MIC2 connects to the parasite actomyosin system through its cytoplasmic tail. MIC2-associated protein (M2AP) binds noncovalently to the MIC2 ectodomain. MIC2 and M2AP are stored in micronemes as proforms. We find that the MIC2-M2AP ectodomain complex is a highly elongated 1:1 monomer with M2AP bound to the TSR6 domain. Crystal structures of N-terminal fragments containing the VWA and TSR1 domains for proMIC2 and MIC2 reveal a closed conformation of the VWA domain and how it associates with the TSR1 domain. A long, proline-rich, disulfide-bonded pigtail loop in TSR1 overlaps the VWA domain. Mannose α-C-linked to Trp-276 in TSR1 has an unusual (1)C4 chair conformation. The MIC2 VWA domain includes a mobile α5-helix and a 22-residue disordered region containing two disulfide bonds in place of an α6-helix. A hydrophobic residue in the prodomain binds to a pocket adjacent to the α7-helix that pistons in opening of the VWA domain to a putative high-affinity state.

PubMed: 24639528
DOI: 10.1073/pnas.1403059111

Experimental method

X-RAY DIFFRACTION (3.2 Å)