Sandbox Reserved 487

From Proteopedia

This Sandbox is Reserved from 13/03/2012, through 01/06/2012 for use in the course "Proteins and Molecular Mechanisms" taught by Robert B. Rose at the North Carolina State University, Raleigh, NC USA. This reservation includes Sandbox Reserved 451 through Sandbox Reserved 500.

To get started:

Click the edit this page tab at the top. Save the page after each step, then edit it again.
Click the 3D button (when editing, above the wikitext box) to insert Jmol.
show the Scene authoring tools, create a molecular scene, and save it. Copy the green link into the page.
Add a description of your scene. Use the buttons above the wikitext box for bold, italics, links, headlines, etc.

More help: Help:Editing

For more help, look at this link: http://www.proteopedia.org/wiki/index.php/Help:Getting_Started_in_Proteopedia

3D Globular Structure of SUMO-2 Protein found in humans with alpha helix labeled in green, beta sheet labeled in dark blue, and hydrophobic residues labeled in light blue

Drag the structure with the mouse to rotate

1 Introduction
2 Structure
3 Mechanism of Action
4 Medical Implications or Possible Application
5 References

Introduction

The SUMO (or Small Ubiquitin-like Modifier) proteins are a group of small proteins that are used to modify cell function through the covalent attachment and detachment from other proteins. These polymers can be attached either as monomers or as lysine-linked polymers where it is attached to a specific lysine side chain on the target protein via an isopeptide bond with its C-terminal glycine. There are four known SUMO proteins found in humans, all of which are used in the trafficking and targeting of proteins. The aforementioned lysine residue modifications are vital to several cellular processes in humans, including DNA replication, DNA repair, mitosis, nuclear transport, and signal transduction. SUMO-modified proteins also serve to increase protein stability as well as aid in transcriptional regulation. SUMO-2 chains found in humans also serve as a signal for proteasomal degradation of modified proteins when subject to polyubiquitination. In addition to the four SUMO proteins found in humans, there are also SUMO relatives found in yeast and other organisms as well as several pseudogenes.

Structure

As mentioned earlier, all SUMO proteins are small and most are around 100 amino acids long depending on what organism they are found in. SUMO-2, which is shown in the structure above, is a globular protein which contains an and a as well as various . Nuclear Magnetic Resonance is the main method used to identify the structure of SUMO. As can be deducted from the name (Small Ubiquitin-like Modifier), SUMO proteins bear great structural resemblance to ubiquitin molecules, even though their amino acid sequences have very little in common.

Mechanism of Action

SUMO proteins attach to their target proteins in various ways, but SUMO attachment (also dubbed SUMOylation) is very similar to ubiquitin attachment. E1 activating enzymes, E2 conjugating enzymes and E3 ligase enzymes act in various pathways to accomplish the conjugation of SUMO. SUMOylation begins with a C-terminal peptide being cleaved by a protease with the use of ATP to create a diglycine motif. The E1 enzyme then becomes bound to the SUMO protein and transitions to the E2 conjugating enzyme. Finally, SUMO is attached to the protein via the E3 ligase enzyme.

Medical Implications or Possible Application

Studies in eukaryotic cells such as the yeast species Saccharomyces cerevisiae and Schizosaccharomyces pombe have shown that SUMO proteins are absolutely essential for the normal functions of the cells. SUMO proteins Smt3 and Pmt3 were found in these yeast cells, and it was discovered that severe growth impairment was a result of deletion of the Pmt3. Additionally, deletion of the Smt3 protein led to decreases in cell viability.

Studies are still being performed regarding the effects of altering the SUMO genes in humans. The SUMO-4 mRNA has been found in human kidneys, lymph nodes, and the spleen, however the endogenous SUMO-4 protein has yet to be found. This raises the question of whether or not SUMO-4 is endogenously expressed or if the SUMO-4 protein precursor must go through the process of maturation in order to conjugate to target proteins. However, substrates of SUMO have been found to be very biomedically important proteins such as tumor suppressor p53, c-jun, PML and huntingtin. SUMO modification also plays a major part in chromosome segregation, regulation of inflammatory response in mammals, and regulation of flowering time in plants.