6y40
From Proteopedia
14-3-3 Sigma in complex with phosphorylated PLN peptide
Structural highlights
DiseasePPLA_HUMAN Defects in PLN are the cause of cardiomyopathy dilated type 1P (CMD1P) [MIM:609909. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.[1] [2] Defects in PLN are the cause of familial hypertrophic cardiomyopathy type 18 (CMH18) [MIM:613874. CMH18 is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.[3] FunctionPPLA_HUMAN Phospholamban has been postulated to regulate the activity of the calcium pump of cardiac sarcoplasmic reticulum. Publication Abstract from PubMedInteractions between a protein and a peptide motif of its protein partner are prevalent in nature. Often, a protein also has multiple interaction partners. X-ray protein crystallography is commonly used to examine these interactions in terms of bond distances and angles as well as to describe hotspots within protein complexes. However, the crystallization process presents a significant bottleneck in structure determination since it often requires notably time-consuming screening procedures, which involve testing a broad range of crystallization conditions via a trial-and-error approach. This difficulty is also increased as each protein-peptide complex does not necessarily crystallize under the same conditions. Here, a new co-crystallization/peptide-soaking method is presented which circumvents the need to return to the initial lengthy crystal screening and optimization processes for each consequent new complex. The 14-3-3sigma protein, which has multiple interacting partners with specific peptidic motifs, was used as a case study. It was found that co-crystals of 14-3-3sigma and a low-affinity peptide from one of its partners, c-Jun, could easily be soaked with another interacting peptide to quickly and easily generate new structures at high resolution. Not only does this significantly reduce the production time, but new 14-3-3-peptide structures that were previously not accessible with the 14-3-3sigma isoform, despite screening hundreds of other different conditions, were now also able to be resolved. The findings achieved in this study may be considered as a supporting and practical guide to potentially enable the acceleration of the crystallization process of any protein-peptide system. A new soaking procedure for X-ray crystallographic structural determination of protein-peptide complexes.,Ballone A, Lau RA, Zweipfenning FPA, Ottmann C Acta Crystallogr F Struct Biol Commun. 2020 Oct 1;76(Pt 10):501-507. doi:, 10.1107/S2053230X2001122X. Epub 2020 Sep 15. PMID:33006579[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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