An expanding universe of small proteins.

Historically, small proteins (sproteins) of less than 50 amino acids, in their final processed forms or genetically encoded as such, have been understudied. However, both serendipity and more recent focused efforts have led to the identification of a number of new sproteins in both Gram-negative and Gram-positive bacteria. Increasing evidence demonstrates that sproteins participate in a wide array of cellular processes and exhibit great diversity in their mechanisms of action, yet general principles of sprotein function are emerging. This review highlights examples of sproteins that participate in cell signaling, act as antibiotics and toxins, and serve as structural proteins. We also describe roles for sproteins in detecting and altering membrane features, acting as chaperones, and regulating the functions of larger proteins.

[1]  R. Losick,et al.  Small Genes under Sporulation Control in the Bacillus subtilis genome , 2010, Journal of bacteriology.

[2]  Robert A. Anderson,et al.  Spermicidal Activity of the Safe Natural Antimicrobial Peptide Subtilosin , 2008, Infectious diseases in obstetrics and gynecology.

[3]  G. Storz,et al.  Small RNAs and Small Proteins Involved in Resistance to Cell Envelope Stress and Acid Shock in Escherichia coli: Analysis of a Bar-Coded Mutant Collection , 2009, Journal of bacteriology.

[4]  S. Delgado,et al.  The Bacteriocin Nisin, an Effective Agent for the Treatment of Staphylococcal Mastitis During Lactation , 2008, Journal of human lactation : official journal of International Lactation Consultant Association.

[5]  H. Vlamakis,et al.  Paracrine signaling in a bacterium. , 2009, Genes & development.

[6]  G. Storz,et al.  Small Toxic Proteins and the Antisense RNAs That Repress Them , 2008, Microbiology and Molecular Biology Reviews.

[7]  R. Losick,et al.  A Small Protein Required for the Switch from σF to σG during Sporulation in Bacillus subtilis , 2010, Journal of bacteriology.

[8]  E. Wagner,et al.  A small SOS‐induced toxin is targeted against the inner membrane in Escherichia coli , 2008, Molecular microbiology.

[9]  D. Schneider,et al.  PetG and PetN, but not PetL, are essential subunits of the cytochrome b6f complex from Synechocystis PCC 6803. , 2007, Research in microbiology.

[10]  R. Losick,et al.  Peptide inhibitor of cytokinesis during sporulation in Bacillus subtilis , 2008, Molecular microbiology.

[11]  T. Stein Bacillus subtilis antibiotics: structures, syntheses and specific functions , 2005, Molecular microbiology.

[12]  R. Losick,et al.  Cannibalism by Sporulating Bacteria , 2003, Science.

[13]  J. Vederas,et al.  Solution structure of carnobacteriocin B2 and implications for structure-activity relationships among type IIa bacteriocins from lactic acid bacteria. , 1999, Biochemistry.

[14]  Aixia Zhang,et al.  Small Stress Response Proteins in Escherichia coli: Proteins Missed by Classical Proteomic Studies , 2009, Journal of bacteriology.

[15]  K. Altendorf,et al.  The KdpF Subunit Is Part of the K+-translocating Kdp Complex of Escherichia coli and Is Responsible for Stabilization of the Complex in Vitro * , 1999, The Journal of Biological Chemistry.

[16]  D. Schneider,et al.  A Regulatory Role of the PetM Subunit in a Cyanobacterial Cytochrome b 6 f Complex* , 2001, The Journal of Biological Chemistry.

[17]  L. Dicks,et al.  Mode of action of lipid II-targeting lantibiotics. , 2005, International journal of food microbiology.

[18]  A. Blanc-Potard,et al.  Hydrophobic peptides: novel regulators within bacterial membrane , 2009, Molecular microbiology.

[19]  V. Nizet,et al.  Staphylococcus epidermidis Antimicrobial δ-Toxin (Phenol-Soluble Modulin-γ) Cooperates with Host Antimicrobial Peptides to Kill Group A Streptococcus , 2010, PloS one.

[20]  M. Goulian,et al.  Feedback Inhibition in the PhoQ/PhoP Signaling System by a Membrane Peptide , 2009, PLoS genetics.

[21]  Jessica M. Silvaggi,et al.  Small Untranslated RNA Antitoxin in Bacillus subtilis , 2005, Journal of bacteriology.

[22]  Pavel A Pevzner,et al.  Imaging mass spectrometry of intraspecies metabolic exchange revealed the cannibalistic factors of Bacillus subtilis , 2010, Proceedings of the National Academy of Sciences.

[23]  T. D. Schneider,et al.  Small membrane proteins found by comparative genomics and ribosome binding site models , 2008, Molecular microbiology.

[24]  M. Vulić,et al.  Ciprofloxacin Causes Persister Formation by Inducing the TisB toxin in Escherichia coli , 2010, PLoS biology.

[25]  E. Koonin,et al.  Abundance of type I toxin–antitoxin systems in bacteria: searches for new candidates and discovery of novel families , 2010, Nucleic acids research.

[26]  Hirotada Mori,et al.  B1500, a small membrane protein, connects the two-component systems EvgS/EvgA and PhoQ/PhoP in Escherichia coli , 2007, Proceedings of the National Academy of Sciences.

[27]  M. Kjos,et al.  An overview of the mosaic bacteriocin pln loci from Lactobacillus plantarum , 2009, Peptides.

[28]  J. Helmann,et al.  The Bacillus subtilis iron-sparing response is mediated by a Fur-regulated small RNA and three small, basic proteins , 2008, Proceedings of the National Academy of Sciences.

[29]  Howard A. Stone,et al.  Geometric Cue for Protein Localization in a Bacterium , 2009, Science.

[30]  E. Chiancone,et al.  Dps proteins prevent Fenton-mediated oxidative damage by trapping hydroxyl radicals within the protein shell. , 2010, Free radical biology & medicine.

[31]  J. Vederas,et al.  Structure of subtilosin A, a cyclic antimicrobial peptide from Bacillus subtilis with unusual sulfur to alpha-carbon cross-links: formation and reduction of alpha-thio-alpha-amino acid derivatives. , 2004, Biochemistry.

[32]  C. K. Vanderpool,et al.  A dual function for a bacterial small RNA: SgrS performs base pairing-dependent regulation and encodes a functional polypeptide , 2007, Proceedings of the National Academy of Sciences.

[33]  W. D. de Vos,et al.  Autoregulation of Nisin Biosynthesis in Lactococcus lactis by Signal Transduction (*) , 1995, The Journal of Biological Chemistry.

[34]  G. Storz,et al.  Repression of small toxic protein synthesis by the Sib and OhsC small RNAs , 2008, Molecular microbiology.

[35]  Véronique Monnet,et al.  A genome-wide survey of short coding sequences in streptococci. , 2007, Microbiology.

[36]  A. Blanc-Potard,et al.  Peptide‐assisted degradation of the Salmonella MgtC virulence factor , 2008, The EMBO journal.

[37]  D. Engelman,et al.  pH-sensitive membrane peptides (pHLIPs) as a novel class of delivery agents , 2010, Molecular membrane biology.

[38]  W. Burkholder,et al.  The histidine kinase inhibitor Sda binds near the site of autophosphorylation and may sterically hinder autophosphorylation and phosphotransfer to Spo0F , 2009, Molecular microbiology.

[39]  Roberto Kolter,et al.  Cannibalism enhances biofilm development in Bacillus subtilis , 2009, Molecular microbiology.

[40]  A. Kennedy,et al.  Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA , 2007, Nature Medicine.

[41]  E. Yamashita,et al.  Structure of the cytochrome b6f complex: quinone analogue inhibitors as ligands of heme cn. , 2007, Journal of molecular biology.

[42]  D. Dubnau,et al.  A peptide signal for adapter protein-mediated degradation by the AAA+ protease ClpCP. , 2007, Molecular cell.

[43]  L. Dicks,et al.  Nisin F in the treatment of respiratory tract infections caused by Staphylococcus aureus , 2009, Letters in applied microbiology.

[44]  Matthew J Bick,et al.  How to switch off a histidine kinase: crystal structure of Geobacillus stearothermophilus KinB with the inhibitor Sda. , 2009, Journal of molecular biology.