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Masayori Inouye

Research & Publications

Toxin-antitoxin (TA) Systems; Their Roles in Bacterial Physiology and the Development of Novel Antibiotics

Almost all bacteria including human pathogens contain suicide or toxin genes, which are induced under stress conditions leading to cell growth arrest and eventual cell death in a way similar to apoptosis or programmed cell death in higher systems. The importance of these toxin genes in medical science was not fully appreciated until recently, when our laboratory and others started to decipher the cellular targets of these toxins and how they inhibit cell growth leading to cell death. Bacterial physiology is considered to be tightly regulated by these toxins and their cognate antitoxins or by the toxin networks under stress conditions. Notably, by taking advantage of the suicidal properties of these toxins, it is possible to develop novel antibiotics against human pathogens. Since Escherichia coli contain more than 13 TA systems, it serves as an ideal paradigm for the study of not only bacterial toxins, but also previously unknown aspects of bacterial physiology governed by the toxin network. Our goal is to decipher structures and functions of the E. coli toxins and study their cellular network. In addition, we are also studying the TA systems in Mycobacterium tuberculosis by identifying their cellular targets and their possible roles in the pathogenecity of this bacterium in human tissues.

  • Zhang, Y., Zhang, J., Hoeflich, K. P., Ikura, M., Qing, G. and Inouye M. (2003) MazF Cleaves Cellular mRNAs Specifically at ACA to Block Protein Synthesis in Escherichia coli . Mol. Cell 12:913-923.
  • Zhang, J., Zhang Y., Zhu, L., Suzuki, M. and Inouye, M. (2004) Interference of mRNA Function by Sequence-specific Endoribonuclease PemK. J. Biol. Chem. 279:20678-20684.
  • Zhang, Y., Zhu, L., Zhang, J. and Inouye, M. (2005) Characterization of ChpBK, an mRNA Interferase from Escherichia coli . J. Biol. Chem. 280:26080-26088.
  • Nariya, H. and Inouye, M. (2008) MazF, an mRNA Interferase, Mediates Programmed Cell Death during Multicellular Myxococcus Development. Cell 132:55-66.
  • Liu, M., Zhang, Y., Inouye, M. and Woychik, W. (2008) Bacterial Addiction Module Toxin Doc Inhibits Translation Elongation through its Association with the 30S Ribosome. Proc. Natl. Acad Sci. USA 105:5885-5890.
  • Li, G.Y., Zhang, Y., Inouye, M. and Ikura, M. (2008) Structural Mechanism of Transcriptional Autorepression of the Escherichia coli RelB/RelE Antitoxin/Toxin Module. J. Mol. Biol. 380:107-119.
  • Prysak, M. H., Mozdzierz, C., Cook, A. M., Zhu, L., Zhang, Y., Inouye, M. and Woychik, N. A. (2009) Bacterial Toxin YafQ is an Endoribonuclease that Associates with the Ribosome and Blocks Translation Elongation through Sequence-specific and Frame-dependent mRNA Cleavage. Mol. Micro. 71:1071-1087.
  • Zhang, Y. and Inouye, M. (2009) The Inhibitory Mechanism of Protein Synthesis by YoeB, an Escherichia coli Toxin. J. Biol. Chem. 284:6627-6638.

mRNA Interferases; Application to Human Diseases
mRNA interferases are encoded by one of the bacterial toxins or suicide genes. MazF from E. coli is the first mRNA interferase discovered in our laboratory and functions as a sequence-specific (ACA) endoribonuclease. Its induction in E. coli cells results in cell growth arrest and eventual cell death. We also observed that its induction in mammalian cells effectively causes Bak (a pro-apoptotic protein)-dependent programmed cell death. We explore the application of bacterial mRNA interferases for mammalian cell growth regulation to develop an effective method for treatment of cancer cells.

  • Zhang, Y., Zhang, J., Haya, H., Kato, I. and Inouye, M. (2005) Insights into the mRNA Cleavage Mechanism by MazF, an mRNA Interferase. J. Biol. Chem. 280:3143-3150.
  • Inouye, M. (2006) The Discovery of mRNA Interferases: Implication in Bacterial Physiology and Application to Biotechnology. J. Cell. Physiol. 209:670-676.
  • Zhu, L., Zhang, Y. L., Teh, J. S., Zhang, J., Connell, N., Rubin, H. and Inouye, M. (2006) Characterization of mRNA Interferases from Mycobacterium tuberculosis . J Biol Chem. 281:18638-43.
  • Shimazu, T., Degenhardt, K., Nur-E-Kamal, A., Zhang, J, Yoshida, T., Zhang, Y.L., Mathew, R., White, E., and Inouye, M. (2007) NBK/BIK Antagonizes MCL-1 and BCL-X L and Activates BAK-mediated Apoptosis in Response to Protein Synthesis Inhibition. Genes Dev. 21:929-941.
  • Zhu, L., Phadtare, S., Nariya, H., Ouyang, M., Husson, R. N. and Inouye, M. (2008) The mRNA Interferases, MazF-mt3 and MazF-mt7 from Mycobacterium tuberculosis Target Unique Pentad Sequences in Single-stranded RNA. Mol. Micro. 69:559-569.
  • Yamaguchi, Y. and Inouye, M. (2009) mRNA Interferases, Sequence-Specific Endoribonucleases from the Toxin–Antitoxin Systems. Prog Nucleic Acid Res Mol Biol. 85:467-500.

Single Protein Production in Living Cells
MazF, an ACA-specific mRNA interferase expression, results in nearly complete degradation of cellular mRNAs, leading to severe reduction of protein synthesis in conjunction with growth arrest. However, most intriguingly, MazF-induced cells are still fully capable of producing a protein at a high level if the mRNA for that protein is engineered to be devoid of all ACA sequences without altering its amino acid sequence. Therefore, we are able to convert E. coli cells into a bioreactor producing a single protein of interest. This system, termed the “ single-protein production” (SPP ) system, is an unprecedented novel technology for structural biology, as when using this technology one does not have to purify a protein of interest for NMR structural study. Thus, this system is especially powerful for the structural study of membrane proteins. We will explore to apply the SPP system for membrane proteins structural study and for protein dynamics in living cells.

  • Suzuki, M., Zhang, J., Liu, M., Woychik, N. and Inouye, M. (2005) Single Protein Production in Living Cells Facilitated by an mRNA Interferase. Mol. Cell 18:253-261.
  • Suzuki, M., Roy , R., Zheng, H., Woychik, N. and Inouye M. (2006) Bacterial Bioreactors for High Yield Production of Recombinant Protein. J. Biol. Chem. 281:37559-37565.
  • Suzuki, M., Mao, L. and Inouye, M. (2007) Single Protein Production (SPP) System in Escherichia coli. Nat Protoc. 2:1802-1810.

Cold-shock Response and Adaptation
When an organism senses downshift in temperature, it responds by eliciting cold-shock response. We use E . coli as a model system to study cold shock response. When the cells encounter cold shock, there is a lag period of growth termed acclimation phase, in which the cellular synthesis of most of the proteins is inhibited as opposed to that of a select group of proteins, termed cold-shock proteins. These proteins help the cells counteract various detrimental cellular changes triggered by the temperature downshift. This is followed by resumption of the cell growth with restoration of synthesis of normal cellular proteins and decrease in the rate of synthesis of cold-shock proteins. E . coli contains a family of nine CspA homologues, CspA being the major cold shock protein. Our studies revealed several unique features of cold-shock expression of CspA and its homologues which act as RNA chaperones to help cold acclimation of cells. We incorporated these novel features to create pCold vectors for production of proteins at low temperature which cannot be produced by the conventional expression systems. Our group is currently focusing on low temperature RNA metabolism involving cold shock proteins such as PNPase, CsdA, and RNase R.

  • Goldstein, J., Pollitt , N. S. and Inouye, M. (1990) The Major Cold Shock Protein of Escherichia coli ; Transcriptional Regulation of its Gene. Proc. Natl. Acad. Sci. USA 87:283-287.
  • Newkirk, K., Feng, W., Jiang, W., Tejero, R., Emerson, S. D., Inouye, M. and Montelione, G. (1994) Solution NMR Structure of the Major Cold shock Proteins (CspA) from Escherichia coli : Identification of a Binding Epitope for DNA. Proc. Natl. Acad. Sci. USA 91:5114-5118.
  • Schindelin, H., Cordes, F., Jiang, W., Inouye, M. and Heinemann, U. (1994) Crystal Structure of the Major Cold Shock Protein of Escherichia coli . Proc. Natl. Acad. Sci. USA 91:5119-5123.
  • Jones, P. and Inouye, M. (1996) RbfA, a 30S-Ribosomal Binding Factor, is a Cold-shock Protein Whose Absence Triggers the Cold-shock Response. Mol. Micro. 21:1207-1218.
  • Jiang, W., Hou, Y. Inouye, M. (1997) CspA, The Major Cold-shock Protein of Escherichia coli , is an RNA Binding Protein. J. Biol. Chem. 272:96-202.
  • Mitta, M., Fang, L. and Inouye, M. (1997) Deletion Analysis of cspA of Escherichia coli : Requirement for the AT-rich UP Element for cspA Transcription and the Downstream Box in the Coding Region for its Cold Shock Induction. Mol. Micro. 26:321-335.
  • Bae, W., Jones, P. G., and Inouye, M. (1997) CspA, the Major Cold-shock Protein of Escherichia coli , Negatively Regulates Its Own Gene Expression. J. Bacteriol. 179:7081-7088.
  • Fang, L., Hou, Y. and Inouye, M. (1998) Role of the Cold-Box Region in the 5' Untranslated Region of the cspA mRNA for Its Transient Expression at Low Temperature in Escherichia coli . J. Bacteriol. 180:90-95.
  • Yamanaka, K., Fang, L., and Inouye M. (1998) The CspA Family of Eschericia coli : Multiple Gene Duplication for Stress Adaptation. Mol. Micro. 27:247-256.
  • Yamanaka, K., Fang, L., and Inouye, M. (1998) The CspA Family of Escherichia coli: Multiple Gene Duplication for Stress Adaptation. Mol. Micro. 27:247-256.
  • Feng W., Tejero, R., Zimmerman, D. E., Inouye, M. and Montelione G. T. (1998) Solution NMR Structure and Backbone Dynamics of the Major Cold-Shock Protein (CspA) from Escherichia coli : Evidence for Conformational Dynamics in the Single-Stranded RNA-binding Site. Biochemistry 37:10881-10896.
  • Bae, W., Phadtare, S., Severinov, K., and Inouye, M. (1999) Characterization of Escherichia coli cspE , whose Product Negativity Regulates Transcription of cspA , the Gene for the Major Cold Shock Protein. Mol. Micro. 31:1429-1441.
  • Phadtare, S., Alsina, J., and Inouye, M. (1999) Cold-Shock Response and Cold-Shock Proteins (Review) Current Opinion in Microbiology Vol 2/2, pp. 175-180.
  • Phadtare, S. and Inouye, M. (1999) Sequences Selective Interactions with RNA by CspB, CspC and CspE, Members of CspA Family of Escherichia coli . Mol. Micro. 33: 1004-1014.
  • Bae, W., Xia, B., Inouye, M. and Severinov, K. (2000) Escherichia coli CspA-Family RNA Chaperones are Transcription Antiterminators. Proc. Nat. Acad. Sci. USA 97:7784-7789.
  • Xia, B., Ke, H. and Inouye, M. (2001) Acquirement of Cold Sensitivity by Quadruple Deletion of the cspA Family and its Suppression by PNPase S1 Domain in Escherichia coli . Mol. Micro. 40:179-188.
  • Xia, B., Etchegaray, J. P. and Inouye, M. (2001) Nonsense Mutations in cspA Cause Ribosome Trapping Leading to Complete Growth Inhibition and Cell Death at Low Temperature in Escherichia coli . J. Biol. Chem. 276:35581-35588.
  • Yamanaka, K., Zheng, W., Crooke, E., Wang, Y.-H. and Inouye, M. (2001) CspD, a Novel DNA Replication Inhibitor Induced during the Stationary Phase in Escherichia coli . Mol. Micro. 39:1572-1584.Inoue, K., Chen, J., Kato, I. and
  • Inouye, M. (2002) Specific Growth Inhibition by Acetate of an Escherichia coli Strain Expressing Era-dE, a Dominant Negative Era Mutant. J. Mol. Micro. Biotech. 4:379-388.
  • Phadtare, S., Inouye, M. and Severinov, K. (2002) The Nucleic Acid Melting Activity of Escherichia coli CspE is Critical for Transcription Antitermination and Cold-acclimation of Cells. J. Biol. Chem. 277:7239-7245.
  • Phadtare, S., Tyagi, S, Inouye, M. and Severinov, K. (2002) Three Amino Acids in Escherichia coli CspE Surface-exposed Aromatic Patch are Critical for Nucleic Acid Melting Activity Leading to Transcription Antitermination and Cold Acclimation of Cells. J. Biol. Chem. 277:46706-46711.
  • Huang, Y. J., Swapna, G. V. T., Rajan, P. K., Ke, H., Xia, B., Shukla, K., Inouye,
    M. and Montelione, G. T. (2003) Solution NMR Structure of Ribosome-binding Factor A (RbfA), A Cold-shock Adaptation Protein from Escherichia coli . J. Mol. Biol. 327:521-536.
  • Xia, B., Ke, H., Shinde, U. and Inouye, M. (2003) The Role of RbfA in 16S rRNA Processing and Cell Growth at Low Temperature in Escherichia coli . J. Mol. Biol. 332:575-584.
  • Phadtare, S., Inouye, M. and Severinov, K. (2004) The Mechanism of Nucleic Acid Melting by a CspA Family Protein. J. Mol. Biol. 337:147-155.
  • Qing, G., Ma, L.-C., Khorchid, A., Swapna, G. V. T., Mal, T. K., Takayama, M. M., Xia, B., Phadtare, S., Ke, H., Acton, T., Montelione, G. T., Ikura, M. and Inouye, M. (2004) Cold-shock Induced High-yield Protein Production in Escherichia coli . Nat Biotech. 22:877-882.
  • Awano, N., Xu, C., Ke, H., Inoue, K., Inouye, M. and Phadtare, S. (2007) Complementation Analysis of the Cold-Sensitive Phenotype of the Escherichia coli csdA Deletion Strain. J. Bacteriol. 189:5808-5815.

Propeptide-mediated Protein Folding; Implication in Human Diseases
The propeptide is an N-terminal extension of a protein which is essential for the folding of the protein. Thus, the propeptides are termed as ‘intramolecular chaperones'. It is known that the propeptide-mediated protein folding plays a crucial role in many important proteins in humans and that mutations in the propeptide can lead to serious human diseases; for example, Val66 to Met mutation in the propeptide of BDNF (brain derived neurotrophic factor) causes misfolding of mature BDNF resulting in a serious defect in human memory. Research of the essential role of the propeptide in protein folding, which was originally discovered in our laboratory in 1987, is thus very important not only for our understanding of the basic principle of protein folding, but also for our understanding of the human diseases caused by propeptide mutations. Using subtilisin as a model system, we study the role of the 77-residue propetide in subtilisin folding by genetic, biochemical and biophysical (including NMR) methods. We are particularly interested in the mechanisms of misfolding caused by mutations in the propeptide termed as ‘protein-memory mutations'.

  • Ikemura, H., Takagi, H., and Inouye, M. (1987) Requirement of Pro Sequence for the Production of Active Subtilisin E in Escherichia coli . J. Biol. Chem. 262: 7859-7864.
  • Zhu, X., Ohta, Y., Jordan , F. and Inouye, M. (1989) Pro sequence of Subtilisin Can Guide the Refolding of Denatured Subtilisin in an Intermolecular Process. Nature 339:483-484.
  • Shinde, U., Li, Y., Chatterjee, S. and Inouye, M. (1993) Folding Pathway Mediated by an Intramolecular Chaperone. Proc. Natl. Acad. Sci. USA 90:6924 6928.
  • Li, Y. and Inouye, M . (1994) Autoprocessing of Prothiolsubtilisin E in Which the Active Site Serine 221 is Altered to Cysteine. J. Biol. Chem. 269:4169-4174.
  • Shinde, U. and Inouye, M. (1995) Folding Mediated by an Intramolecular Chaperone: Autoprocessing Pathway of the Precursor Resolved Via a `Substrate assisted Catalysis' Mechanism. J. Mol. Biol. 247:390-395.
  • Shinde, U. and Inouye, M. (1995) Folding Pathway Mediated by an Intramolecular Chaperone: Characterization of the Structural Changes in Pro subtilisin E Coincident with Autoprocessing. J. Mol. Biol. 252:25-30.
  • Shinde, U. P., Liu, J. J. and Inouye, M. (1997) Protein Memory through Altered Folding Mediated by Intramolecular Chaperones. Nature 398:520-522.
  • Jain, S. C., Shinde, U., Li, Y., Inouye, M . and Berman, H. M. (1998) The Crystal Structure of an Autoprocessed Ser221Cys-subtilisin E-Propeptide Complex at 2.0 A Resolution. J. Mol. Biol. 284:137-144.
  • Shinde, U. P., Fu, X., and Inouye, M. (1999) A Pathway for Conformational Diversity in Proteins Mediated by Intramolecular Chaperones. J. Biol. Chem. 274:15615-15621.
  • Fu, X., Inouye, M. and Shinde, U. (2000) Folding Pathway Mediated by an Intramolecular Chaperone: The Inhibitory and Chaperone Functions of the Subtilisin Propeptide are not Obligatorily Linked. J. Biol. Chem. 275:16871-16878.
  • Inouye, M. , Fu, X. and Shinde, U. (2001) Substrate-Induced Activation of a Trapped IMC-Mediated Protein Folding Intermediate. Nat. Struct. Biol. 8:321-325.
  • Sone, M., Falzon, L. and Inouye, M. (2005) The Role of Tryptophan Residues in the Autoprocessing of Prosubtilisin E. Biochim Biophys Acta - Proteins and Proteomics 1749:15-22.
  • Falzon, L., Suzuki, M., Inouye, M. (2006) Finding One of a Kind: Advances in Single-protein Production. Curr Opin Biotechnol. 17:347-352.
  • Falzon, L., Patel, S., Chen, Y.J., Inouye, M. (2007) Autotomic Behavior of the Propeptide in Propeptide-mediated Folding of Prosubtilisin E. J. Mol. Biol. 366:494-503.
  • Chen, Y. J. and Inouye, M. (2008) The Intramolecular Chaperone-mediated Protein Folding. Curr. Opin. Struct. Biol. 6:765-770.

Sensory Histidine Kinases
Histidine kinases play a major role as sensory proteins in adaptation to external stress signals in bacteria. Our group was the first to determine the three-dimensional structure of the cytoplasmic domain of a transmembrane histidine kinase. We focus our effort on the structural and functional studies on an E. coli histidine kinase, termed “EnvZ”, to understand how an external signal is transduced across the membrane to regulate its kinase activity. We are also interested in the interaction of EnvZ with OmpR, as OmpR phosphorylated by EnvZ is the essential transcription factor for reciprocal transcription of ompF and ompC.

  • Utsumi, R., Brissette, R. E., Rampersaud, A., Forst, S. A., Oosawa, K. and Inouye, M. (1989) Activation of Bacterial Porin Gene Expression by a Chimeric Signal Transducer in Response to Aspartate. Science 245:1246-1249.
  • Yang, Y., and Inouye, M. (1991) Intermolecular Complementation between Two Defective Mutants of Escherichia coli Signal Transducing Receptors. Proc. Natl. Acad. Sci. USA 88:11057-11061.
  • Yang, Y. and Inouye, M. (1993) Requirement of Both Kinase and Phosphatase Activites of an Escherichia coli Receptor (Taz1) for Ligand dependent Signal Transduction. J. Mol. Biol. 231:335-342.
  • Yang, Y., Park, H. and Inouye, M. (1993) Ligand Binding Induces Asymmetrical Transmembrane Signal through a Receptor Dimer. J. Mol. Biol. 232:493-498.
  • Rampersaud, A., Harlocker, S. and Inouye, M. (1994) The OmpR Protein of Escherichia coli Binds to Sites in the ompF Promoter Region in a Hierarchical Manner Determined by Its Degree of Phosphorylation. J. Biol. Chem. 269:12559-12566.
  • Harlocker, S., Bergstrom, L. and Inouye, M. (1995) Tandem Binding of Six OmpR Proteins to the ompF Upstream Regulatory Sequence of Escherichia coli . J. Biol. Chem. 270:26849-26856.
  • Dutta, R. and Inouye, M. (1996) Reverse Phosphotransfer from OmpR to EnvZ in a Kinase-Phosphatase+ Mutant of EnvZ (EnvZ-N347D), a Bifunctional Signal Transducer of Escherichia coli . J. Biol. Chem. 271:1424-1429.
  • Egger, L. A., Park, H. and Inouye, M. (1997) Review: Signal Transduction via the Histidyl-aspartyl Phosphorelay. Genes to Cells 2:167-184.
  • Park, H., Saha, S. K. and Inouye, M. (1998) Two-domain Reconstitution of a Functional Protein Histidine Kinase. Proc. Natl. Acad. Sci. USA 95:6728-6732.
  • Tanaka, T., Saha, S.K., Tomomori, C., Ishima, R., Liu, D., Tong, K. I., Park, H., Dutta, R., Qin, L., Swindells, M. B., Yamazaki, T., Ono, A. M., Kainosho, M., Inouye, M. and Ikura, M. (1998) NMR Structure of the Histidine Kinase Domain of the Escherichia coli Osmosensor EnvZ. Nature 396:88-92.
  • Tomomori, C., Tanaka, T., Dutta, R., Park, H., Saha, S. K., Zhu, Y., Ishima, R., Liu, D., Tong, K. I., Kurokawa, H., Qian, H., Inouye, M. , and Ikura, M. (1999) Solution Structure of the Homodimeric Core Domain of Escherichia coli Histidine Kinase EnvZ. Nat. Struct. Biol. 6:729-734.
  • Zhu, Y., Qin, L., Yoshida, T., and Inouye, M. (2000) Phosphatase Activity of Histidine Kinase EnvZ without Kinase Catalytic Domain. Proc. Nat. Acad. Sci. USA 97:7808-7813.
  • Cai, S. J. and Inouye, M. (2002) EnvZ-OmpR Interaction and Osmoregulation in Escherichia coli . J. Biol. Chem 277:24155-24161
  • Zhu, Y. and Inouye, M. (2002) The Role of the G2 Box, a Conserved Motif in Histidine Kinase Superfamily, in Modulating the Function of EnvZ. Mol. Micro. 45:653-663.
  • Yoshida, T., Cai, S.-J., Inouye, M. (2002) Interaction of EnvZ, a Sensory Histidine kinase, with Phosphorylated OmpR, the Cognate Response Regulator. Mol. Micro. 46:1283-94.
  • Yoshida, T., Qin, L. and Inouye, M. (2002) Formation of the Stoichiometric Complex of EnvZ, a Histidine Kinase, with its Response Regulator, OmpR. Mol. Micro. 46:1273-1282.
  • Cai, S.-J., Khorchid, A., Ikura, M. and Inouye, M. (2003) Probing Catalytically Essential Domain Orientation in Histidine Kinase EnvZ by Targeted Disulfide Crosslinking. J. Mol. Biol. 328:409-418.
  • Zhu, Y. and Inouye, M. (2003) Analysis of the Role of the EnvZ Linker Region in Signal Transduction Using a Chimeric Tar/EnvZ Receptor Protein, Tez1. J. Biol. Chem. 278:22812-22819.
  • Zhu Y. and Inouye, M. (2004) The HAMP Linker in Histidine Kinase Dimeric Receptors is Critical for Symmetric Transmembrane Signal Transduction. J Biol Chem. 279:48152-48158.
  • Yoshida, T., Qin, L., Egger, L. A., Inouye, M. (2006) Transcription Regulation of ompC and ompR by a Single Transcription Factor, OmpR. J. Biol. Chem. 281:17114-17123.
  • Inouye, M. (2006) Signalling by Transmembrane Proteins Shifts Gears. Cell: 126:829-831.
  • Kishii, R., Falzon, L., Yoshida, T., Kobayashi, H. and Inouye, M. (2007) Structural and Functional Studies of the HAMP Domain of EnvZ, an Osmosensing Transmembrane Histidine Kinase in Escherichia coli . J. Biol. Chem. 282:26401-26408.

Collagens consist of approximately 25% of protein mass of the human body. There are essential structural proteins in the bone, tendon, cartilage, skin, blood vessel and mechanical support of all known tissues and organs. Interestingly, a large number of bacteria produce collagen-like proteins without using hydroxyproline, a major amino acid component of human collagens. In collaboration with Dr. Barbara Brodsky, Professor of Biochemistry, we were able to produce a number of bacterial collagens from various bacteria in a large quantity in E. coli . In addition to the biochemical characterization of these bacterial collagens, we are exploring to use them as biomaterials for medical use substantiating animal collagens.

  • Mohs, A., Silva, T., Yoshida, T., Amin, R., Lukomski, S., Inouye, M. and Brodsky, B. (2007) Mechanism of Stabilization of a Bacterial Collagen Triple-Helix in the Absence of Hydroxyproline”. J. Bacteriol. 282:29757-29765.