ISCB-Asia/SCCG 2012 Keynote Address
Prof. Gunnar von Heijne
Stockholm University

Coming to grips with membrane proteins  

Photo Max Brouwers


Integral membrane proteins account for around 30% of all proteins in most organisms. They are key players (and favored drug targets) in all processes dealing with transport of molecules or ions across cellular membranes, as well as in signal transduction pathways. Yet, our understanding of membrane proteins lags behind that of soluble proteins in almost every respect: biosynthesis, folding, structure, and function. In the past 10 years, however, membrane proteins have progressively moved into the headlines of the molecular life sciences, in a large part thanks to a tight interplay between bioinformatics, computational modeling, and wet-lab work ranging from biophysics to structural biology.

The goal of our own work is to provide quantitative data on the energetics and kinetics of membrane protein assembly in vivo to serve as a basis both for a deeper understanding of the mechanism of membrane protein assembly, and to help improve topology- and structure-prediction methods.


Prof. Heijne has worked mainly on problems related to protein sorting and membrane protein biogenesis and structure. The work includes both bioinformatics methods development (e.g. methods for prediction of signal peptides and other sorting signals as well as prediction of membrane protein topology) and experimental studies in E. coli and eukaryotic systems.

The most important achievements include the discovery and experimental validation of the so-called “(-1,-3)-rule” (describes signal peptide cleavage sites; EJB 133:17, JMB 184:99) and the “positive inside” rule (describes membrane protein topology; EMBO J 5:3021, Nature 341:456, Cell 62:1135, Cell 77:401), the development of widely used prediction methods (e.g., TopPred, SignalP, TargetP, TMHMM; JMB 225:487, Prot.Engineer. 10:1, JMB 300:1005, JMB 305:567, JMB 327:735, JMB 340:783, PNAS 105:7177), the first proteome-wide theoretical and experimental studies of membrane protein topology in E. coli and S. cerevisiae (Protein Sci. 7:1029, Science 308:1321, JMB 35:489, PNAS 103:11142), the first quantitative analysis of the energetics of membrane protein assembly in vivo (Nature 433:377, Science 307:1427, Nature 450:1026, PNAS 106:11588), and recent theoretical and experimental studies of so-called dual-topology membrane proteins and their role in the evolution of membrane protein structure (Nature Struct.Mol.Biol. 13:112, Science 315:1282, Science 328:1698).

Altogether, the cumulated work has been cited ~46,000 times, h-index = 85 (Web of Science). Listed in the ISI Highly Cited database.

Prof. Heijne has recieved numerous awards, including the 2012 ISCB Senior Scientist Award.