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Solution Structures of Engineered Vault Particles

26 Pages Posted: 11 Apr 2018 Publication Status: Published

See all articles by Ke Ding

Ke Ding

University of California, Los Angeles (UCLA) - Department of Bioengineering

Xing Zhang

University of California, Los Angeles (UCLA) - California Nanosystems Institute

Jan Mrazek

University of California, Los Angeles (UCLA) - Department of Biological Chemistry

Valerie A. Kickhoefer

University of California, Los Angeles (UCLA) - Department of Biological Chemistry

Mason Lai

University of California, Los Angeles (UCLA) - Department of Microbiology, Immunology and Molecular Genetics

Hwee L. Ng

University of California, Los Angeles (UCLA) - Division of Infectious Diseases

Otto O. Yang

University of California, Los Angeles (UCLA) - California Nanosystems Institute

Leonard H. Rome

University of California, Los Angeles (UCLA) - California Nanosystems Institute

Z. Hong Zhou

University of California, Los Angeles (UCLA) - Department of Bioengineering

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Abstract

Prior crystal structures of the vault have provided clues of its structural variability but are non-conclusive due to crystal packing. Here, we obtained vaults by engineering at the N-terminus of rat major vault protein (MVP) an HIV-1 Gag protein segment and determined their near-atomic resolution structures in non-crystalline/solution environment. Vaults in solution adopt two conformations, 1 and 2, both with D39 symmetry. From N- to C-terminus, each MVP monomer is organized into three regions: body, shoulder and cap. While conformer 1 is identical to one of the crystal structures, the shoulder in conformation 2 is translocated up to 10 Å along the symmetry axis, resulting in an outward-projected cap. Our structures clarify the conformation discrepancies in the body domain in the prior crystallography models. The vault’s drug-delivery potential is highlighted by the internal localization and structural flexibility of its Gag-loaded N-terminal extension at the waist region of the engineered vault.

Suggested Citation

Ding, Ke and Zhang, Xing and Mrazek, Jan and Kickhoefer, Valerie A. and Lai, Mason and Ng, Hwee L. and Yang, Otto O. and Rome, Leonard H. and Zhou, Z. Hong, Solution Structures of Engineered Vault Particles (2018). Available at SSRN: https://ssrn.com/abstract=3155840 or http://dx.doi.org/10.2139/ssrn.3155840
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Ke Ding

University of California, Los Angeles (UCLA) - Department of Bioengineering

410 Westwood Plaza
Los Angeles, CA 90095-160
United States

Xing Zhang

University of California, Los Angeles (UCLA) - California Nanosystems Institute

570 Westwood Plaza
Building 114
Los Angeles, CA 90095
United States

Jan Mrazek

University of California, Los Angeles (UCLA) - Department of Biological Chemistry

615 Charles E Young Drive South
Los Angeles, CA 90095-1737
United States

Valerie A. Kickhoefer

University of California, Los Angeles (UCLA) - Department of Biological Chemistry

615 Charles E Young Drive South
Los Angeles, CA 90095-1737
United States

Mason Lai

University of California, Los Angeles (UCLA) - Department of Microbiology, Immunology and Molecular Genetics

1602 Molecular Sciences Building
609 Charles E. Young Drive, East
Los Angeles, CA 90095
United States

Hwee L. Ng

University of California, Los Angeles (UCLA) - Division of Infectious Diseases

200 Medical Plaza, Suite 365-C
Los Angeles, CA 90095
United States

Otto O. Yang

University of California, Los Angeles (UCLA) - California Nanosystems Institute

570 Westwood Plaza
Building 114
Los Angeles, CA 90095
United States

Leonard H. Rome

University of California, Los Angeles (UCLA) - California Nanosystems Institute

570 Westwood Plaza
Building 114
Los Angeles, CA 90095
United States

Z. Hong Zhou (Contact Author)

University of California, Los Angeles (UCLA) - Department of Bioengineering ( email )

410 Westwood Plaza
Los Angeles, CA 90095-160
United States

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