Ruprecht-Karls-Universität Heidelberg
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Cell Chemistry

Prof. Dr. Sabine Strahl

Prof. Dr. Sabine Strahl
Prof. Dr. Sabine Strahl
Im Neuenheimer Feld 360
69120 Heidelberg
Fon +49 6221 54-6286
Fax +49 6221 54-5859
ed.grebledieh-inu.soc TEA lharts.enibas

The Strahl Lab - Glycobiology: Sweet Science

Glycosylation is one of the most abundant and complex protein modifications known. In many biological systems more than half of all proteins are glycosylated and glycan chains are highly crucial for a wide range of biological processes. Our laboratory is interested in various aspects of glycobiology in eukaryotic organisms with a main focus on O-mannosylation, an evolutionarily conserved, essential protein modification with immense impact on a variety of cellular processes. Having identified the first protein O-mannosyltransferase PMT1 in the model organism yeast, our work has substantially contributed to the understanding of protein O-mannosylation in eukaryotes. The laboratory continues to work on the molecular organization of the O-mannosylation machinery in the ER and the role of O-mannosyl glycans for growth and developement.

Protein O-Mannosylation, an essential modification that is conserved from yeast to human

Figure2r.jpgO-mannosyl glycans are short linear oligosaccharides linked via an alpha-glycosidically-bound mannose to Ser and Thr residues. Biosynthesis is initiated at the endoplasmic reticulum (ER) by the transfer of mannose from dolichyl phosphate-activated mannose to Ser or Thr residues of proteins that are entering the secretory pathway. Further chain elongation takes place in the Golgi apparatus using nucleotide-activated sugars as donors.

The initial mannosyltransfer reaction is catalyzed by an essential family of Dol-P-mannose:protein O-mannosyltransferases (PMTs) that is evolutionarily conserved from yeast to humans. Focusing on PMTs we aim to understand how the ER O-mannosylation machinery works. Further, we analyze the functions of O-mannosyl glycans in eukaryotic model systems.

Research Projects

Structure and dynamics of the protein O-mannosylation machinery
The role of protein O-mannosylation in the unfolded protein response
Protein O-mannosylation in mammals

Latest Publications

Neubert P, Halim A, Zauser M, Essig A, Joshi HJ, Zatorska E, Larsen IS, Loibl M, Castells-Ballester J, Aebi M, Clausen H, Strahl S (2016)
Mapping the O-mannose glycoproteome in Saccharomyces cerevisiae
Molecular & Cellular Proteomics [Epub ahead of print]


Halim A, Larsen ISB, Neubert P, Joshi HJ, Petersen BL, Vakhrusheva SY, Strahl S, Clausen H (2015)
Discovery of a nucleocytoplasmic O-mannose glycoproteome in yeast
Proc Natl Acad Sci U S A 112:15648-53


Structure and dynamics of the protein O-mannosylation machinery SFB638

Protein translocation in the endoplasmic reticulum (ER) and protein glycosylation are intimately connected, fundamental processes essential for the normal functioning of eukaryotic cells. Nascent polypeptide chains of secretory and membrane proteins are N-glycosylated and O-mannosylated while they are translocated across the ER membrane. The translocation and concurrent N-glycosylation of these proteins take place on a large molecular machine, the translocon complex (TC), which is associated with membrane-bound polysomes. O-mannosylation antecedes N-glycosylation and competes for substrate proteins, suggesting that the O-mannosylation machinery is associated with the TC.

In order to understand the molecular basis of coupling protein translocation and N-glycosylation with protein O-mannosylation we aim to elucidate i) the molecular architecture of the O-mannosylation machinery and ii) its macromolecular association with the TC complex in the yeast Saccharomyces cerevisiae.

People involved: Jakob Engel, Martin Loibl, Ewa Zatorska, Anke Metschies

The role of protein O-mannosylation in the unfolded protein response SFB1036

In all eukaryotes the proper folding and maturation of proteins in the endoplasmic reticulum (ER) is both aided and monitored by a number of chaperones and folding enzymes in a complex process referred to as ER quality control (QC). ER-QC is compromised under a variety of conditions, collectively termed ER stress, which cause the accumulation of misfolded proteins in the ER lumen. Eukaryotic cells cope with ER stress by activating a multi-layered protective response, the unfolded protein response (UPR), which adapts the secretory pathway to the ER protein load and increases the efficiency of protein folding. In fungi and animals, O-mannosylation is an essential protein modification that is initiated in the ER by a conserved family of protein O-mannosyltransferases (PMTs). It was recently observed that O-mannosylation of membrane and secretory proteins is especially crucial during ER stress; however, molecular functions and mechanisms are poorly understood.

In this project we want to dissect the role of protein O-mannosylation with respect to ER homeostasis during stress conditions. During the first funding period we are planning to i) define the physiological role of O-mannosyl glycans during ER stress using a proteome wide approach; ii) analyze O-mannosylation as fail-safe mechanism increasing the solubility of aberrant ER proteins; iii) characterize the features of PMTs in the context of ER protein maturation during the UPR.

People involved: Joan Castells-Ballester, Patrick Neubert, Anke Metschies

Structural and functional characterization of O-mannosyl glycans in mammals Baden-Württemberg Stiftung

Protein O-mannosylation is conserved from yeast to humans and defines a new pathomechanism of neuromuscular diseases. Until recently, only a handful of O-mannosylated proteins had been identified, but all of them are of fundamental importance for cell-cell and cell-matrix interactions. The main reason why so few O-mannosylated proteins have been characterized so far is a lack of tools to specifically detect O-mannosyl glycans.

The aim of this project is i) to establish specific tools for the detection of O-mannosyl glycans; ii) to analyze the occurrence and the distribution of O-mannosyl glycans bearing glycoproteins in mammals; and iii) to identify new O-mannosylated proteins in mouse and human, and to analyze structure and function of the O-mannosyl glycans. The results of this project will improve the understanding of protein O-mannosylation in mammals and improve the diagnosis of early O-mannosylation defects in human.

People involved: Markus Bartels, Patrick Winterhalter

/var/www/cos/ / Prof. Dr. Sabine Strahl _e