The progress of membrane protein structure determination

Abstract

The rate of membrane protein (MP) structure determination has been examined for the 18-year period following the publication of the first high-resolution crystal structure. The growth is solidly exponential, but lags behind the rate for soluble proteins during the equivalent time period.

Richard Dickerson, writing in 1978 (PDB Newsletter 2002), estimated that the structures of about 132 soluble proteins had been determined to sufficient resolution for the backbone to be traced. From a plot of the number of new structures per year (n) versus years (y), he determined that n = exp(ay) with a = 0.19. This growth rate predicted about 13,000 structures by 2001—which turned out to be remarkably accurate. Dickerson’s letter was written 18 years after the publication (Kendrew et al. 1960) of the first high-resolution protein structure in 1960. The same amount of time has now elapsed since the publication (Deisenhofer et al. 1985) of the first high-resolution structure of a membrane protein (MP) in 1985. What has our progress been in this challenging field relative to soluble proteins, and what might the future hold?

Using data from the database of membrane proteins of known 3D structure that my laboratory maintains (see URL in legend, Fig. 1 ▶), there were 75 unique MP structures at the close of 2003. An analysis similar to Dickerson’s yields a = 0.14 (data not shown). The 18-year cumulative exponential growths of new structures for both soluble and membrane proteins are shown in Figure 1 ▶. The growth rate suggests that we can expect the number of new MP structures to exceed 100 some time in 2005; and by 2025, about 2200.

Figure 1.

Cumulative totals of new structures since publication of the first high-resolution crystallographic structures. The data for soluble proteins (red squares) are from a letter written in 1978 by Richard Dickerson (http://www.rcsb.org/pdb/dickerson_letter.html). The data for MPs (solid blue circles) were compiled from data available at http://blanco.biomol.uci.edu/Membrane_Proteins_xtal.html. “New” MP structures includes the same protein from different organisms, but excludes structures of mutagenized versions of proteins already in the database. Structures that differ only by the substrate bound or by physiological state are also excluded. The solid curves are fits of the data to the equation m = exp(by), where m is the cumulative total of new structures and y is the number of years since the publication of the first structure. The parameter b = 0.289 and 0.242 for soluble and for MPs, respectively. The data for MPs suggest that there will be more than 100 structures some time in 2005.