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Protein Sci. 2019 Sep;28(9):1676-1689. doi: 10.1002/pro.3683. Epub 2019 Aug 2.

Structures of single-layer β-sheet proteins evolved from β-hairpin repeats.

Xu Q1,2,3, Biancalana M4, Grant JC1, Chiu HJ1,2, Jaroszewski L1,5,6,7, Knuth MW1,8, Lesley SA1,8,9,10, Godzik A1,5,6,7, Elsliger MA1,9, Deacon AM1,2,11, Wilson IA1,9.

Author information

1
Joint Center for Structural Genomics, www.jcsg.org.
2
Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, California.
3
GMCA@APS, Argonne National Laboratory, Lemont, Illinois.
4
Perlmutter Cancer Center, New York University Langone Medical Center, Smilow Research Center, New York, New York.
5
Center for Research in Biological Systems, University of California, La Jolla, California.
6
Program on Bioinformatics and Systems Biology, Sanford-Burnham Medical Research Institute, La Jolla, California.
7
Division of Biomedical Sciences, University of California, Riverside, California.
8
Protein Sciences Department, Genomics Institute of the Novartis Research Foundation, San Diego, California.
9
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California.
10
Merck & Co., Inc., South San Francisco, California.
11
Accelero Biostructures, San Carlos, California.

Abstract

Free-standing single-layer β-sheets are extremely rare in naturally occurring proteins, even though β-sheet motifs are ubiquitous. Here we report the crystal structures of three homologous, single-layer, anti-parallel β-sheet proteins, comprised of three or four twisted β-hairpin repeats. The structures reveal that, in addition to the hydrogen bond network characteristic of β-sheets, additional hydrophobic interactions mediated by small clusters of residues adjacent to the turns likely play a significant role in the structural stability and compensate for the lack of a compact hydrophobic core. These structures enabled identification of a family of secreted proteins that are broadly distributed in bacteria from the human gut microbiome and are putatively involved in the metabolism of complex carbohydrates. A conserved surface patch, rich in solvent-exposed tyrosine residues, was identified on the concave surface of the β-sheet. These new modular single-layer β-sheet proteins may serve as a new model system for studying folding and design of β-rich proteins.

KEYWORDS:

human gut microbiome; protein folding; secreted proteins; single-layer β-sheet proteins; structural genomics; β-hairpin repeats

PMID:
31306512
DOI:
10.1002/pro.3683

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