Crystal structures of human Torsin-A and methods of determining and using the same
A protein composition including TorsinA or TorsinA mutant, LULL1, and a nanobody obtained by immunization using TorsinA and LULL1 is used to grow complex crystals, and three dimensional structures are determined using x-ray data of the crystals. A screening platform is built based on the determined three dimensional structures for designing a drug lead to cure dystonia.
1. A protein composition, comprising: a target protein; a modulator of the target protein; and a nanobody comprising a polypeptide as set forth in SEQ ID NO: 5 or a portion thereof, wherein said nanobody or said portion thereof specifically binds to at least one of the target protein and the modulator.
2. The protein composition of claim 1 , wherein the target protein is TorsinA, a mutant of TorsinA, or a portion thereof.
3. The protein composition of claim 2 , wherein the target protein comprises an amino acid sequence as set forth in at least one of SEQ ID NO: 1-3 or a portion thereof.
4. The protein composition of claim 1 , wherein the modulator is LULL1 or a portion thereof.
5. The protein composition of claim 4 , wherein the modulator comprises the amino acid sequence set forth in the SEQ ID NO: 4.
6. The protein composition of claim 1 , wherein the nanobody is specific for a complex comprising the target protein and the modulator.
7. The protein composition of claim 6 , wherein the nanobody is obtained by immunization using the target protein comprising the amino acid sequence set forth in the SEQ ID NO: 2 and the modulator comprising the amino acid sequence set forth in the SEQ ID NO: 4.
8. The protein composition of claim 7 , wherein the target protein comprises the amino acid sequence set forth in at least one of SEQ ID NO: 1-3 or a portion thereof, the modulator comprises the amino acid sequence set forth in the SEQ ID NO: 4 or a portion thereof, the nanobody comprises the amino acid sequence set forth in the SEQ ID NO: 5 or a portion thereof, and the protein composition is co-expressed, and optionally purified together.