MYRbase: analysis of genome-wide glycine myristoylation enlarges the functional spectrum of eukaryotic myristoylated proteins

Abstract

We evaluated the evolutionary conservation of glycine myristoylation within eukaryotic sequences. Our large-scale cross-genome analyses, available as MYRbase, show that the functional spectrum of myristoylated proteins is currently largely underestimated. We give experimental evidence for in vitro myristoylation of selected predictions. Furthermore, we classify five membrane-attachment factors that occur most frequently in combination with, or even replacing, myristoyl anchors, as some protein family examples show.

Figure 1

Power-law distribution of family clusters in MYRbase with maximal 40% sequence identity and a minimal size of 3 (to exclude false positives). The inset table gives the values and correlation coefficients for different minimal cluster sizes. The power function distribution (without shift along the argument axis x), the Pareto distribution and the Zipf's law (if the rank is approximated by the argument x) have the common analytical form y = a · x^b. Such distributions generally occur as the limit distribution of a multiplicative stochastic process with a lower boundary constraint (here, minimal cluster size). The common phenomenological form does not imply a unified mechanism for generating samples obeying these distribution functions. We suggest interpreting cluster size in terms of time for evolutionary divergence within the cluster (see text).

Figure 2

Schematic representation of the membrane attachment of proteins with a myristoyl anchor (dark gray, space-filling atomic representation) in combination with different co-occurring membrane-attachment factors (coMAFs). Class I, plus palmitoyl anchor (also dark gray, space-filling); class II, plus cluster of positive charges (dark blue, spacefill); class III, plus PIP₂-specific binding domain (PIP₂ in space-filling, alkyl tails in cyan); class IV, plus transmembrane segments; class V, plus a domain for specific protein-membrane protein interactions. White space-filling molecules in the model membrane represent cholesterol and symbolize targeting to specialized compartments. Two different states of the calcium/myristoyl-switch of recoverin are depicted in the lower left of the figure (calcium ions in red). Visualization is with SwissPdb-Viewer [108].