Biochemistry & Biophysics

Ry Young

young Professor of Biochemistry and Biophysics and of Biology
Program in Microbial Genetics and Genomics

Phone: (979) 845-2087
Email: ryland@tamu.edu
Visit the Young lab Home Page
or see the Practical Genomics for Undergraduates website

A.B. Rice University (1968)
Ph.D. University of Texas, Dallas (1975)
Postdoc. Harvard Medical School (1975-78)

Joined Texas A&M faculty in 1978

The Molecules and Mechanisms of Bacteriophage Lysis
Most bacterial viruses (phages) cause lysis of their host cell to release the progeny virions. Large phages elaborate an enzyme ("endolysin") to degrade the cell wall and also a small membrane protein ("holin"). The holin accumulates in the membrane and then, at a precisely scheduled time, suddenly forms a hole to allow release of endolysin through the cytoplasmic membrane to gain access to the wall. We use molecular genetics and biochemistry to study how this small protein is able to act as a molecular "clock" and punch holes in membranes. Small phages make single proteins which cause host lysis in a different way. This strategy is to target the host cell wall synthesis machinery; that is, the virus makes a "protein antibiotic" that causes lysis in the same way as antibiotics like penicillin by inhibiting an enzyme in the multi-step pathway of murein biosynthesis. Thus, when the infected cell tries to divide, it blows up, or lyses, because it can't make the new cell wall between the daughter cells. Remarkably, each of three different, small phages blocks a different step in the pathway. These small lysis proteins are models for a completely new class of antibacterial antibiotics. Also, the E. coli SlyD protein is required for this mode of lysis in one case. SlyD is a member of an ubiquitous family of proteins related to human "immunophilins," the targets of immune-suppression drugs. We study SlyD to learn about the role of this class of proteins in biology.

Recent Publications
  1. White R, Tran TA, Dankenbring CA, Deaton J & Young R (2009) The N-terminal transmembrane domain of {lambda} S is required for holin but not antiholin function. J Bacteriol
  2. Summer EJ, Enderle CJ, Ahern SJ, Gill JJ, Torres CP, Appel DN, Black MC, Young R & Gonzalez CF (2009) Genomic and biological analysis of phage Xfas53 and related prophages of Xylella fastidiosa. J Bacteriol
  3. Sun Q, Kuty GF, Arockiasamy A, Xu M, Young R & Sacchettini JC (2009) Regulation of a muralytic enzyme by dynamic membrane topology. Nat Struct Mol Biol 16: 1192-4
  4. Pang T, Savva CG, Fleming KG, Struck DK & Young R (2009) Structure of the lethal phage pinhole. Proc Natl Acad Sci U S A 106: 18966-71
  5. Dewey JS, Struck DK & Young R (2009) Thiol protection in membrane protein purifications: a study with phage holins. Anal Biochem 390: 221-3
  6. Zheng Y, Struck DK & Young R (2009) Purification and functional characterization of phiX174 lysis protein E. Biochemistry 48: 4999-5006
  7. Zheng Y, Struck DK, Bernhardt TG & Young R (2008) Genetic analysis of MraY inhibition by the phiX174 protein E. Genetics 180: 1459-66
  8. Berry J, Summer EJ, Struck DK & Young R (2008) The final step in the phage infection cycle: the Rz and Rz1 lysis proteins link the inner and outer membranes. Mol Microbiol 70: 341-51
  9. Young RF 3rd (2008) Molecular biology. Secret weapon. Science 321: 922-3
  10. Zheng Y, Struck DK, Dankenbring CA & Young R (2008) Evolutionary dominance of holin lysis systems derives from superior genetic malleability. Microbiology 154: 1710-8
  11. Summer EJ, Berry J, Tran TA, Niu L, Struck DK & Young R (2007) Rz/Rz1 lysis gene equivalents in phages of Gram-negative hosts. J Mol Biol 373: 1098-112
  12. Park T, Struck DK, Dankenbring CA & Young R (2007) The pinholin of lambdoid phage 21: control of lysis by membrane depolarization. J Bacteriol 189: 9135-9
  13. Summer EJ, Gill JJ, Upton C, Gonzalez CF & Young R (2007) Role of phages in the pathogenesis of Burkholderia, or 'Where are the toxin genes in Burkholderia phages?'. Curr Opin Microbiol 10: 410-7
  14. Tran TA, Struck DK & Young R (2007) The T4 RI antiholin has an N-terminal signal anchor release domain that targets it for degradation by DegP. J Bacteriol 189: 7618-25
  15. Park T, Struck DK, Deaton JF & Young R (2006) Topological dynamics of holins in programmed bacterial lysis. Proc Natl Acad Sci U S A 103: 19713-8
  16. Young R, Henkin TM & Turnbough CL Jr (2006) The phage meeting: Classical venue, new momentum. J Bacteriol 188: 4597-600
  17. Summer EJ, Gonzalez CF, Bomer M, Carlile T, Embry A, Kucherka AM, Lee J, Mebane L, Morrison WC, Mark L, King MD, LiPuma JJ, Vidaver AK & Young R (2006) Divergence and mosaicism among virulent soil phages of the Burkholderia cepacia complex. J Bacteriol 188: 255-68
  18. Tran TA, Struck DK & Young R (2005) Periplasmic domains define holin-antiholin interactions in t4 lysis inhibition. J Bacteriol 187: 6631-40
  19. Xu M, Arulandu A, Struck DK, Swanson S, Sacchettini JC & Young R (2005) Disulfide isomerization after membrane release of its SAR domain activates P1 lysozyme. Science 307: 113-7
  20. Deaton J, Savva CG, Sun J, Holzenburg A, Berry J & Young R (2004) Solubilization and delivery by GroEL of megadalton complexes of the lambda holin. Protein Sci 13: 1778-86

Links for Courtesy Access Publications
Molecular Biology. Secret Weapon Summary or Full text
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