Crystal structures of human Torsin-A and methods of determining and using the same

Patent metadata

Field	Value
Publication number	US-9823250-B2
Application number	US-201715442639-A
Country	US
Kind code	B2
Filing date	Feb 25, 2017
Priority date	Feb 25, 2016
Publication date	Nov 21, 2017
Grant date	Nov 21, 2017

Abstract

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.

First claim

What is claimed is:

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.

Assignees

• Massachusetts Inst Technology

Inventors

• Schwartz Thomas U
• Demircioglu F Esra
• Sosa-Alvarado Brian A

Classifications

• G01N23/20

  by using diffraction of the radiation by the materials, e.g. for investigating crystal structure; by using scattering of the radiation by the materials, e.g. for investigating non-crystalline materials; by using reflection of the radiation by the materials · CPC title

• G06F19/18

  Physics · mapped topic

• G01N2333/914

  Hydrolases (3) · CPC title

• C12Y306/04

  acting on acid anhydrides; involved in cellular and subcellular movement (3.6.4) · CPC title

• C40B30/02

  Chemistry & Metallurgy · mapped topic