Solving a complex protein problem

Feb 14, 2014
Figure 1: A computerized reconstruction of microscope data showing the endoplasmic reticulum (red) and exit sites (green) where transport vesicles are produced. Credit: Kazuo Kurokawa/RIKEN Center for Advanced Photonics

Many proteins undergo processing within cellular compartments called the endoplasmic reticulum and the Golgi apparatus. Transit between these structures is facilitated by transport vesicles, which bubble out from the membranes of these compartments with the help of specialized coat proteins (Fig. 1). While most proteins, or 'cargo', marked for transport are gathered up by direct interaction with the coat proteins, some only interact with coat proteins through intermediary 'cargo receptor' complexes.

Akihiko Nakano, Ryogo Hirata and colleagues from the RIKEN Center for Advanced Photonics have now revealed the composition of these cargo receptor complexes—an important starting point for understanding their distinct roles. "It remains largely unknown how cargo receptors recognize their specific cargo proteins," explains Hirata, "because only small numbers of cargo-receptor-dependent cargo proteins have been identified."

The researchers focused on the p24 cargo receptor complexes, which contain either two or four subunits. Yeast cells have eight known p24 proteins, representing four subfamilies. These include single p24β and p24δ proteins, both mandatory for p24 function, and three different p24α and p24γ proteins each. As the relative contribution of each of these latter proteins was unclear, Hirata and his colleagues generated yeast strains lacking different combinations of p24α and p24γ. The loss of any single subfamily member only had a mild effect, but the loss of two, or all three, proved much more disruptive to transport, demonstrating an important contribution from these subfamilies. "We showed that the major functional p24 complexes are tetramers containing one each of an α, β, γ and δ subunit," says Hirata. The researchers also discovered an additional p24δ subunit—Rrt6—which had been identified in previous research as a protein of unknown function.

To further dissect these complexes, the researchers examined how the subunits preferentially interact with each other and determined that only 6 out of the 18 possible α–β–γ–δ combinations typically assemble within yeast cells. Preliminary analysis suggests that there is considerable overlap in the function of these various complexes, but Hirata notes that distinct roles may emerge as new cargoes are identified. "We are now trying to identify isoform-specific cargo proteins," he says. "We have found a few candidates from past p24 studies and are going to examine these first." In the meantime, Hirata believes that the results will offer valuable guidance for future functional studies by giving researchers a useful schematic for how the various p24 subunits actually assemble within the cell.

Explore further: Tracing the protein assembly line

More information: Hirata, R., Nihei, C. & Nakano, A. "Isoform-selective oligomer formation of Saccharomyces cerevisiae p24 family proteins." The Journal of Biological Chemistry 288, 37057–37070 (2013).

add to favorites email to friend print save as pdf

Related Stories

The complexity of regulated development in plants

Mar 15, 2013

In most living organisms, growth and development are controlled by selective modification of the lifespans of particular proteins. This mechanism is especially prevalent in plants, allowing rapid moderation ...

Putting light-harvesters on the spot

Oct 19, 2011

How the light-harvesting complexes required for photosynthesis get to their site of action in the plant cell is reported by RUB biologists in the Journal of Biological Chemistry. The team led by Prof. Dr. Danja Schunemann has de ...

Tracing the protein assembly line

Dec 20, 2013

Many newly synthesized proteins undergo a sequence of enzymatic modifications that enable them to do their jobs better. This process occurs within a series of membrane-bound structures called 'cisternae' ...

Some motor proteins cooperate better than others

Jan 09, 2014

Rice University researchers have engineered cells to characterize how sensitively altering the cooperative functions of motor proteins can regulate the transport of organelles.

Plants recycle too

Feb 13, 2014

A research team from VIB and Ghent University (Belgium), and Staffan Persson from the Max Planck Institute of Molecular Plant Physiology in Potsdam (Germany) has now identified a new protein complex which is crucial for endocytosis ...

Recommended for you

Building the ideal rest stop for protons

16 hours ago

Where protons, or positive charges, decide to rest makes the difference between proceeding towards ammonia (NH3) production or not, according to scientists at Pacific Northwest National Laboratory (PNNL) and ...

Cagey material acts as alcohol factory

17 hours ago

Some chemical conversions are harder than others. Refining natural gas into an easy-to-transport, easy-to-store liquid alcohol has so far been a logistic and economic challenge. But now, a new material, designed ...

User comments : 0