PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
Header Icons
E-Collection

Related Articles
Community-Nominated Targets
July 2015
Drug Discovery: Solving the Structure of an Anti-hypertension Drug Target
July 2015
Retrospective: 7,000 Structures Closer to Understanding Biology
July 2015
Design and Evolution: Unveiling Translocator Proteins
June 2015
Signaling with DivL
May 2015
Signaling: A Platform for Opposing Functions
May 2015
Signaling: Securing Lipid-Protein Partnership
May 2015
Dynamic DnaK
March 2015
Iron-Sulfur Cluster Biosynthesis
December 2014
Mitochondrion: Flipping for UCP2
December 2014
Mitochondrion: Setting a New TRAP1
December 2014
Power in Numbers
August 2014
Quorum Sensing: A Groovy New Component
August 2014
Quorum Sensing: E. coli Gets Involved
August 2014
iTRAQing the Ubiquitinome
July 2014
Microbiome: The Dynamics of Infection
September 2013
Protein-Nucleic Acid Interaction: A Modified SAM to Modify tRNA
July 2013
Protein-Nucleic Acid Interaction: Versatile Glutamate
July 2013
PDZ Domains
April 2013
Alpha-Catenin Connections
March 2013
Cell-Cell Interaction: A FERM Connection
March 2013
Cell-Cell Interaction: Magic Structure from Microcrystals
March 2013
Cell-Cell Interaction: Modulating Self Recognition Affinity
March 2013
Bacterial Hemophores
January 2013
Archaeal Lipids
December 2012
Membrane Proteome: Capturing Multiple Conformations
December 2012
Lethal Tendencies
October 2012
Symmetry from Asymmetry
October 2012
A signal sensing switch
September 2012
Regulatory insights
September 2012
AlkB Homologs
August 2012
Budding ensemble
August 2012
Targeting Enzyme Function with Structural Genomics
July 2012
The machines behind the spindle assembly checkpoint
June 2012
Chaperone interactions
April 2012
Pilus Assembly Protein TadZ
April 2012
Revealing the Nuclear Pore Complex
March 2012
Topping off the proteasome
March 2012
Twist to open
March 2012
Disordered Proteins
February 2012
Analyzing an allergen
January 2012
Making Lipopolysaccharide
January 2012
Pulling on loose ends
January 2012
Terminal activation
December 2011
The Perils of Protein Secretion
November 2011
Bacterial Armor
October 2011
TLR4 regulation: heads or tails?
October 2011
Ribose production on demand
September 2011
Moving some metal
August 2011
Looking for lipids
July 2011
Ribofuranosyl Binding Protein
June 2011
A molecular switch for neuronal growth
May 2011
Cell wall recycler
May 2011
Added benefits
April 2011
NMR challenges current protein hydration dogma
March 2011
Nitrile Reductase QueF
March 2011
Tip formin
March 2011
Inhibiting factor
February 2011
PASK staying active
February 2011
Tryptophanyl-tRNA Synthetase
February 2011
Regulating nitrogen assimilation
January 2011
Subtle shifts
January 2011
Nitrobindin
December 2010
Function following form
October 2010
tRNA Isopentenyltransferase MiaA
August 2010
Importance of extension for integrin
June 2010
Phytochrome
April 2010
Alg13 Subunit of N-Acetylglucosamine Transferase
February 2010
Hemolysin BL
January 2010
Secretagogin
December 2009
Two-component signaling
December 2009
Network coverage
November 2009
Pseudouridine Synthase TruA
November 2009
Unusual cell division
October 2009
Toxin-antitoxin VapBC-5
September 2009
Salicylic Acid Binding Protein 2
August 2009
Proofreading RNA
July 2009
Ykul structure solves bacterial signaling puzzle
July 2009
Hda and DNA Replication
June 2009
Controlling p53
May 2009
Mitotic checkpoint control
May 2009
Ribonuclease and Ribonuclease Inhibitor
April 2009
The elusive helicase
April 2009
Aquaglyceroporin
March 2009
High-energy storage system
February 2009
A new class of bacterial E3 ubiquitination enzymes
January 2009
Poly(A) RNA recognition
January 2009
Activating BAX
December 2008
Scavenger Decapping Enzyme DcpS
November 2008
Bacteriophage Lambda cII Protein
October 2008
New metal-binding domain
October 2008
Blocking AmtB
September 2008
T-Rex
September 2008
Aspartate Dehydrogenase
August 2008
RNase T
July 2008
Chronophin
May 2008

Research Themes Cell biology

Bacteriophage Lambda cII Protein

PSI-SGKB [doi:10.3942/psi_sgkb/fm_2008_10]
Featured System - October 2008
Short description: Living cells are constantly making decisions: when to eat, when to move, even when to die.

1zs4 Living cells are constantly making decisions: when to eat, when to move, even when to die. Viruses must also make decisions, but at a much simpler level. This simplicity makes them the perfect subjects for study of regulatory networks. The lambda bacteriophage has been a favorite of scientists, since it only needs to make one big decision during its life cycle. Usually, it follows a lytic life cycle: it enters cells, forces the cell to make many copies of itself, and finally bursts out of the cell, ready to infect more cells. However, if times are lean, the bacteriophage can decide to switch to a less violent approach. In the lysogenic phase, it integrates its genome into the bacterial genome, and then it is replicated each time the bacteria divides. It hitchhikes in the bacterial genome until some signal, such as DNA damage, causes it to switch back to the lytic phase and continue its campaign of destruction.

Decisions, Decisions

Several proteins together make the decision about which type of life cycle is best for the current situation. At the center of this regulatory network are the cI repressor and cro proteins. Together they form a switch, with cI repressor maintaining the lysogenic state and cro initiating the lytic state. The cII protein is the "final arbiter" of the decision, flipping this switch to the lysogenic state if the conditions warrant it. When the time is right, cII protein binds to three promoters in the bacteriophage genome, which leads to expression of the cI repressor and a DNA integrase enzyme, and inhibition of Q, a key protein in the lytic state, and the DNA excision enzyme.

Breaking Symmetry

Researchers have been studying the cII protein for decades, and have anxiously awaited a look at the structure of this interesting protein. The cII protein poses two mysteries in molecular recognition. It is a tetramer of four identical chains, but it binds to promoters with only two repeats, with the sequence TTGCNNNNNNTTGC. Also, since these two repeats are tandem repeats, and not palindromic, the protein can't be perfectly symmetrical. In collaboration with Seth Darst's laboratory at the Rockefeller University in New York, researchers at the Midwest Center for Structural Genomics have obtained the first look at how this protein recognizes its DNA promoter, solving both of these mysteries with structures of the protein alone and the protein bound to a short piece of DNA. The cII protein contains DNA-binding domains that are connected together with flexible linkers that allow them to break symmetry and find the best orientation on the two TTGC repeats. The four chains associate into two dimers, and in each dimer, only one of the chains actually contacts the DNA.

Promoter Recognition

The DNA-binding domains make specific contacts with all four base pairs in the TTGC recognition sequence, reading the arrangement of DNA atoms in the major groove. These include hydrophobic interactions with the methyl group on the thymines, and hydrogen bonds with the cytosines and guanines (some using a water molecule as intermediary). To take a closer look at this complex interaction, the JSmol tab below displays an interactive JSmol.

HutI Imidazolonepropionase

Two structures capture HutI at the beginning and the end of its reaction. This Jmol image shows a close-up of the active site and you can switch between the two structures using the buttons below. PDB entry 2q09 is bound to an analogue of the substrate. A water molecule (large turquoise sphere) is positioned over the ring in the substrate. An iron ion (brown sphere) activates the water. Two histidines and a glutamine (in green) assist in the dehydration reaction, and three histidines and an aspa

References

  1. Jian, D., Kim, Y., Maxwell, K.L., Beasley, S., Zhang, R., Gussin, G.N., Edwards, A. M. and Darst, S.A. (2005) Crystal structure of bacteriophage lambda cII and its DNA complex. Molecular Cell 19, 259-269.

  2. Dodd, I.B., Shearwin, K.E. and Egan, J.B. (2005) Revisited gene regulation in bacteriophage lambda. Current Opinion in Genetics and Development 15, 145-152.

  3. Oppenheim, A.B., Kobiler, O., Stavans, J., Court,D.L. and Adhya, S. (2005) Switches in bacteriophage lambda development. Annual Review of Genetics 39, 409-429.

Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health