The Molecule of the Month series, by David S.
Goodsell, explores the functions and
significance of selected biological macromolecules for a general
audience. These installments are available at
www.rcsb.org/pdb/molecules/molecule_list.html. A sample of the molecules featured during this past quarter are included below:
July, 2003 -- Your body is a democratic nation of cells. Each cell is an individual with its
own needs, but all of your cells work together to keep you alive. As you might imagine, this
requires an incredible amount of cooperation. Cells are in constant communication to inform
their neighbors of their needs and future plans. They send messages to each other, passing
hormones and chemokines and other molecular messages from cell to cell. These messages are
received by proteins in the cell membrane, which transmit the signal inside. There, a
bewilderingly complex collection of proteins relays the message to all of the appropriate
places inside the cell.
The Src protein, shown in PDB entry 2src, is a signaling protein that specializes in
messages that control the growth of cells. It sits just inside the cell membrane, where it
assists in the passing of signals from various protein receptors to the proteins that turn
"on" the engines of protein synthesis and cellular growth. Src is a tyrosine kinase, so it
relays its messages by adding phosphate groups to special tyrosine amino acids in protein
chains. It adds phosphate groups to a wide variety of proteins that control cellular
structure, cell communication, and cellular growth, turning them "on" and releasing them to
perform their individual tasks.
For more information about Src tyrosine kinase, see
Calmodulin: Sensing Calcium
August, 2003 -- Calcium is the most plentiful mineral element found in your body, with
phosphorous coming in second. This probably doesn't come as a surprise, since your bones are
strengthened and supported by about two kilograms of calcium and phosphorous. Your body also
uses a small amount of calcium, in the form of calcium ions, to perform more active duties.
Calcium ions play essential roles in cell signaling, helping to control processes such as
muscle contraction, nerve signaling, fertilization and cell division. Through the action of
calcium pumps and several kinds of calcium binding proteins, cells keep their internal
calcium levels 1000-10,000 times lower than the calcium levels in the blood. Thus when
calcium is released into cells, it can interact with calcium sensing proteins and trigger
different biological effects, causing a muscle to contract, releasing insulin from the
pancreas, or blocking the entry of additional sperm cells once an egg has been fertilized.
As its name suggests, calmodulin is a CALcium MODULated proteIN. It is abundant in the
cytoplasm of all higher cells and has been highly conserved through evolution. Calmodulin
acts as an intermediary protein that senses calcium levels and relays signals to various
calcium-sensitive enzymes, ion channels and other proteins. Calmodulin is a small
dumbbell-shaped protein composed of two globular domains connected together by a flexible
linker. Each end binds to two calcium ions. PDB entry 3cln has all four sites filled with
calcium ions and the linker has formed a long alpha helix separating the two calcium-binding
For more information on calmodulin, see www.rcsb.org/pdb/molecules/pdb44_2.html.
Estrogen Receptor: a Large Family
PDB ID: 1hcq
J.W. Schwabe, L. Chapman, J.T. Finch, D. Rhodes (1993): The crystal structure of the estrogen receptor DNA-binding domain bound to DNA: how receptors discriminate between their response elements. Cell 75, pp. 567-78.
September, 2003 -- Estrogens are small, carbon-rich molecules built from cholesterol. This
is quite different than larger hormones, such as insulin and growth hormone, which are
sensed by receptors on the cell surface. Estrogens pass directly into cells throughout the
body, so the cell can use receptors that are in the nucleus, right at the site of action on
the DNA. When estrogen enters the nucleus, it binds to the estrogen receptor, causing it to
pair up and form a dimer. This dimer then binds to several dozen specific sites in the DNA,
strategically placed next to the genes that need to be activated. Then, the DNA-bound
receptor activates the DNA-reading machinery and starts the production of messenger RNA.
When researchers looked into the human genome, they found over 150 proteins that are similar
to the estrogen receptor. This is a large family of nuclear receptors that sense the levels
of small hormones and other signaling molecules, such as steroid and thyroid hormones,
vitamin D, and retinoic acid. Like estrogen, these are all small molecules that pass
directly into cells and find their way to the nucleus. These receptors each bind to a
specific signaling molecule and then activate or repress their own set of 50-100 genes. For
more information on nuclear receptors from a genomic perspective, take a look at the Protein
of the Month feature at the European Bioinformatics Institute.
For more information about the estrogen receptor, see
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