Prof. Dr. Irmgard Sinning
Heidelberg University Biochemistry Center
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Heidelberg Researchers Decode Key Component of Cellular Protein Transport System

Press Release No. 61/2014
4 April 2014
Central element of signal recognition particle characterised through structural biology
Forschung Srp68 460x175

Illustration: K. Wild, Abteilung Strukturbiologie

Structure of human SRP68 (blue) with SRP RNA (green) and SRP19 (light blue). Inserting the “strong ARM” (arrow) bends the RNA and pushes the two bases on the opposite side outward (orange). These modifications are essential for SRP function in protein translocation.

In their research on cellular protein transport, Heidelberg researchers have succeeded in characterising the structure and function of another important element of this complex transport system. At centre stage is the signal recognition particle, or SRP, the molecular “postman” for the sorting and membrane insertion of proteins. The team led by Prof. Dr. Irmgard Sinning of the Heidelberg University Biochemistry Center was now able to decode an important and so far not characterised SRP component. The results of this research were published today in “Science”.

Every cell contains hundreds of proteins, more than a third of which must be sorted out for incorporation into cell membranes or export from the cell. SRP is the molecular “postman” responsible for this process. Cellular traffic falls apart without SRP logistics. With the aid of a built-in transport signal, SRP packages are retrieved right at the ribosomes, the synthesis factories of the cell. From there they go to the outbox, the translocation channel. In the human organism, SRP is a macromolecular complex consisting of a ribonucleic acid, the SRP RNA, and six proteins bound to it. While four of these proteins are understood at the atomic-detail level, the two largest ones – SRP68 and SRP72 – had “stubbornly resisted closer study,” explains Prof. Sinning.

The Structural Biology department headed by Irmgard Sinning has now succeeded in characterising an essential component of the SRP system, the RNA binding domain of SRP68. The Heidelberg researchers were focussed on how this protein binds to SRP RNA. They discovered that SRP68 has an arginine-rich motif (ARM), which is not only responsible for binding, but also significantly alters the structure of the SRP RNA. The “strong ARM” bends the RNA into its functional form. “Without this modification, the SRP would not be able to bind to the ribosomes correctly, which would block transport of newly synthesized proteins to the translocation channel,” adds Prof. Sinning.

The analysis of earlier electron microscopy and biochemical data allows for even further conclusions. Bending the RNA pushes two bases outward, which make direct contact with the ribosome. Once the translocation channel is reached, the contact breaks off, and these bases are available for regulating the motor system of translocation. “Our research on the ‘strong ARM’ of protein translocation allowed us to fill in one of the last remaining gaps of the SRP system,” underscores Dr. Klemens Wild from Prof. Sinning’s department.

Original publication:
J.T. Grotwinkel, K. Wild, B. Segnitz and I. Sinning: SRP RNA Remodeling by SRP68 Explains Its Role in Protein Translocation, Science (4 April 2014), Vol. 344 no. 6179 pp. 101-104, doi: 10.1126/science.1249094

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