skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Structures of single-layer {beta}-sheet proteins evolved from {beta}-hairpin repeats

Journal Article · · Protein Science
DOI:https://doi.org/10.1002/pro.3683· OSTI ID:1574395

Free-standing single-layer beta-sheets are extremely rare in naturally occurring proteins, even though beta-sheet motifs are ubiquitous. Here we report the crystal structures of three homologous, single-layer, anti-parallel beta-sheet proteins, comprised of three or four twisted beta-hairpin repeats. The structures reveal that, in addition to the hydrogen bond network characteristic of beta-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 beta-sheet. These new modular single-layer beta-sheet proteins may serve as a new model system for studying folding and design of beta-rich proteins.

Research Organization:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Organization:
National Institutes of Health (NIH)
DOE Contract Number:
AC02-06CH11357
OSTI ID:
1574395
Journal Information:
Protein Science, Vol. 28, Issue 9
Country of Publication:
United States
Language:
English

References (56)

Converging concepts of protein folding in vitro and in vivo journal June 2009
The Protein-Folding Problem, 50 Years On journal November 2012
RepeatsDB: a database of tandem repeat protein structures journal December 2013
Protein Repeats: Structures, Functions, and Evolution journal May 2001
A recurring theme in protein engineering: the design, stability and folding of repeat proteins journal August 2005
Repeat-protein folding: New insights into origins of cooperativity, stability, and topology journal January 2008
Classification of β-hairpin repeat proteins journal February 2018
Tryptophan zippers: Stable, monomeric  -hairpins journal May 2001
10 Residue Folded Peptide Designed by Segment Statistics journal August 2004
β-hairpin-forming peptides; models of early stages of protein folding journal September 2010
A stable single-layer β-sheet without a hydrophoe journal February 1998
Crystal structure of Lyme disease antigen outer surface protein A complexed with an Fab journal April 1997
Crystal structures of the CPAP/STIL complex reveal its role in centriole assembly and human microcephaly journal September 2013
Structural Analysis of the G-Box Domain of the Microcephaly Protein CPAP Suggests a Role in Centriole Architecture journal November 2013
The BC component of ABC toxins is an RHS-repeat-containing protein encapsulation device journal August 2013
The centriolar protein CPAP G-box: an amyloid fibril in a single domain journal October 2015
Topographical and Temporal Diversity of the Human Skin Microbiome journal May 2009
Expansion of the Protein Repertoire in Newly Explored Environments: Human Gut Microbiome Specific Protein Families journal June 2010
Structural genomics of the Thermotoga maritima proteome implemented in a high-throughput structure determination pipeline journal August 2002
Identification, classification, and analysis of beta-bulges in proteins journal October 1993
Searching protein structure databases with DaliLite v.3 journal September 2008
The crystal structure of mouse VDAC1 at 2.3 A resolution reveals mechanistic insights into metabolite gating journal November 2008
Atomic-resolution crystal structure of Borrelia burgdorferi outer surface protein A via surface engineering journal August 2006
Role of Tryptophan−Tryptophan Interactions in Trpzip β-Hairpin Formation, Structure, and Stability journal November 2009
A mechanism of covalent substrate binding in the x-ray structure of subunit K of the Escherichia coli dihydroxyacetone kinase journal June 2003
Hydrophobic Surface Burial Is the Major Stability Determinant of a Flat, Single-layer β-Sheet journal April 2007
Exact and efficient analytical calculation of the accessible surface areas and their gradients for macromolecules journal February 1998
Tryptophan residues: Scarce in proteins but strong stabilizers of β-hairpin peptides journal January 2010
Bacteroides cellulosilyticus sp. nov., a cellulolytic bacterium from the human gut microbial community journal July 2007
Glycan Foraging in Vivo by an Intestine-Adapted Bacterial Symbiont journal March 2005
Functional Genomic and Metabolic Studies of the Adaptations of a Prominent Adult Human Gut Symbiont, Bacteroides thetaiotaomicron , to the Suckling Period journal September 2006
A new subfamily of bacterial ABC-type transport systems catalyzing export of drugs and carbohydrates journal October 1992
Carbohydrate-binding modules: fine-tuning polysaccharide recognition journal September 2004
Recent structural studies of carbohydrate-binding modules journal November 2006
Inference of Macromolecular Assemblies from Crystalline State journal September 2007
Natural  -sheet proteins use negative design to avoid edge-to-edge aggregation journal March 2002
Model systems for β-hairpins and β-sheets journal August 2006
Combining the polymerase incomplete primer extension method for cloning and mutagenesis with microscreening to accelerate structural genomics efforts journal January 2008
Improved Prediction of Signal Peptides: SignalP 3.0 journal July 2004
Atomic Structures of the Human Immunophilin FKBP-12 Complexes with FK506 and Rapamycin journal January 1993
An approach to rapid protein crystallization using nanodroplets journal March 2002
An automated system to mount cryo-cooled protein crystals on a synchrotron beamline, using compact sample cassettes and a small-scale robot journal November 2002
A short history of SHELX journal December 2007
The Buccaneer software for automated model building. 1. Tracing protein chains journal August 2006
Coot model-building tools for molecular graphics journal November 2004
REFMAC 5 for the refinement of macromolecular crystal structures journal March 2011
GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit journal February 2013
ProDy: Protein Dynamics Inferred from Theory and Experiments journal April 2011
PROMOTIF-A program to identify and analyze structural motifs in proteins journal February 1996
Matt: Local Flexibility Aids Protein Multiple Structure Alignment journal January 2008
TM-align: a protein structure alignment algorithm based on the TM-score journal April 2005
MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability journal January 2013
TeXshade: shading and labeling of multiple sequence alignments using LaTeX2e journal February 2000
Recognition of spatial motifs in protein structures 1 1Edited by J. Thornton journal January 1999
PISCES: a protein sequence culling server journal August 2003
Systematic discovery of pseudomonad genetic factors involved in sensitivity to tailocins journal March 2021

Similar Records

Structures of single-layer β-sheet proteins evolved from β-hairpin repeats
Journal Article · Mon Jul 15 00:00:00 EDT 2019 · Protein Science · OSTI ID:1574395

sup 1 H NMR identification of a. beta. -sheet structure and description of folding topology in putidaredoxin
Journal Article · Tue Apr 23 00:00:00 EDT 1991 · Biochemistry; (United States) · OSTI ID:1574395

Minimalist design of water-soluble cross-[beta] architecture
Journal Article · Fri Aug 13 00:00:00 EDT 2010 · Proc. Natl. Acad. Sci. USA · OSTI ID:1574395