Accurate computational design of multipass transmembrane proteins

Author:

Lu Peilong12ORCID,Min Duyoung3ORCID,DiMaio Frank12ORCID,Wei Kathy Y.12,Vahey Michael D.4ORCID,Boyken Scott E.12ORCID,Chen Zibo12ORCID,Fallas Jorge A.12,Ueda George12ORCID,Sheffler William12,Mulligan Vikram Khipple12ORCID,Xu Wenqing5,Bowie James U.3,Baker David126ORCID

Affiliation:

1. Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.

2. Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.

3. Department of Chemistry and Biochemistry, UCLA-DOE Institute, Molecular Biology Institute, University of California, Los Angeles (UCLA), CA 90095, USA.

4. Department of Bioengineering and Biophysics Group, University of California, Berkeley, Berkeley, CA 94720, USA.

5. Department of Biological Structure, University of Washington, Seattle, WA 98195, USA.

6. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.

Abstract

Membrane protein oligomers by design In recent years, soluble protein design has achieved successes such as artificial enzymes and large protein cages. Membrane proteins present a considerable design challenge, but here too there have been advances, including the design of a zinc-transporting tetramer. Lu et al. report the design of stable transmembrane monomers, homodimers, trimers, and tetramers with up to eight membrane-spanning regions in an oligomer. The designed proteins adopted the target oligomerization state and localized to the predicted cellular membranes, and crystal structures of the designed dimer and tetramer reflected the design models. Science , this issue p. 1042

Funder

National Institutes of Health

Howard Hughes Medical Institute

National Research Foundation of Korea

Raymond and Beverly Sackler fellowship

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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