5wrw

From Proteopedia

Structure of human apo-SRP72

PDB ID 5wrw

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Structural highlights

5wrw is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.91Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

SRP72_HUMAN Autosomal dominant aplasia and myelodysplasia. The disease is caused by mutations affecting the gene represented in this entry.

Function

SRP72_HUMAN Signal-recognition-particle assembly has a crucial role in targeting secretory proteins to the rough endoplasmic reticulum membrane. Binds the 7S RNA only in presence of SRP68. This ribonucleoprotein complex might interact directly with the docking protein in the ER membrane and possibly participate in the elongation arrest function.

Publication Abstract from PubMed

The co-translational targeting or insertion of secretory and membrane proteins into the endoplasmic reticulum (ER) is a key biological process mediated by the signal recognition particle (SRP). In eukaryotes, the SRP68-SRP72 (SRP68/72) heterodimer plays an essential role in protein translocation. However, structural information on the two largest SRP proteins, SRP68 and SRP72, is limited, especially regarding their interaction. Herein, we report the first crystal structures of human apo-SRP72 and the SRP68/72 complex at 2.91A and 1.7A resolution, respectively. The SRP68-binding domain of SRP72 contains four atypical tetratricopeptide repeats (TPR) and a flexible C-terminal cap. Apo-SRP72 exists mainly as dimers in solution. To bind to SRP68, the SRP72 homodimer disassociates, and the indispensable C-terminal cap undergoes a pronounced conformational change to assist formation of the SRP68/72 heterodimer. A 23-residue polypeptide of SRP68 is sufficient for tight binding to SRP72 through its unusually hydrophobic and extended surface. Structural, biophysical, and mutagenesis analyses revealed that cancer-associated mutations disrupt the SRP68-SRP72 interaction and their co-localization with ER in mammalian cells. The results highlight the essential role of the SRP68-SRP72 interaction in SRP-mediated protein translocation and provide a structural basis for disease diagnosis, pathophysiology, and drug design.

Human apo-SRP72 and SRP68/72 complex structures reveal the molecular basis of protein translocation.,Gao Y, Zhang Q, Lang Y, Liu Y, Dong X, Chen Z, Tian W, Tang J, Wu W, Tong Y, Chen Z J Mol Cell Biol. 2017 Jun 1;9(3):220-230. doi: 10.1093/jmcb/mjx010. PMID:28369529^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gao Y, Zhang Q, Lang Y, Liu Y, Dong X, Chen Z, Tian W, Tang J, Wu W, Tong Y, Chen Z. Human apo-SRP72 and SRP68/72 complex structures reveal the molecular basis of protein translocation. J Mol Cell Biol. 2017 Jun 1;9(3):220-230. doi: 10.1093/jmcb/mjx010. PMID:28369529 doi:http://dx.doi.org/10.1093/jmcb/mjx010