2YMY

Structure of the murine Nore1-Sarah domain

Summary for 2YMY

• Entry DOI: 10.2210/pdb2ymy/pdb
• Related: 2FNF
• Descriptor: RAS ASSOCIATION DOMAIN-CONTAINING PROTEIN 5, CADMIUM ION (3 entities in total)
• Functional Keywords: apoptosis, tumor suppressor, coiled-coil, ras association domain family
• Biological source: MUS MUSCULUS (HOUSE MOUSE)
• Cellular location: Cytoplasm (By similarity): Q5EBH1
• Total number of polymer chains: 2
• Total formula weight: 11267.59

Authors

Makbul, C.,Schwarz, D.,Aruxandei, D.C.,Wolf, E.,Hofmann, E.,Herrmann, C. (deposition date: 2012-10-10, release date: 2013-03-20, Last modification date: 2024-05-08)

Primary citation

Makbul, C.,Constantinescu Aruxandei, D.,Hofmann, E.,Schwarz, D.,Wolf, E.,Herrmann, C.
Structural and Thermodynamic Characterization of Nore1-Sarah: A Small, Helical Module Important in Signal Transduction Networks.
Biochemistry, 52:1045-, 2013

PubMed Abstract: Tumor suppressor Nore1, its acronym coming from novel Ras effector, is one of the 10 members of the Rassf (Ras association domain family) protein family that have been identified. It is expressed as two mRNA splice variants, Nore1A and a shorter isoform, Nore1B. It forms homo- and heterocomplexes through its C-terminal SARAH (Sav/Rassf/Hpo) domain. The oligomeric state of Nore1 and other SARAH domain-containing proteins is important for their cellular activities. However, there are few experimental data addressing the structural and biophysical characterization of these domains. In this study, we show that the recombinant SARAH domain of Nore1 crystallizes as an antiparallel homodimer with representative characteristics of coiled coils. As is typical for coiled coils, the SARAH domain shows a heptad register, yet the heptad register is interrupted by two stutters. The comparisons of the heptad register of Nore1-SARAH with the primary structure of Rassf1-4, Rassf6, MST1, MST2, and WW45 indicate that these proteins have a heptad register interrupted by two stutters, too. Moreover, on the basis of the structure of Nore1-SARAH, we also generate structural models for Rassf1 and Rassf3. These models indicate that Rassf1- and Rassf3-SARAH form structures very similar to that of Nore1-SARAH. In addition, we show that, as we have previously found for MST1, the SARAH domain of Nore1 undergoes association-dependent folding. Nevertheless, the Nore1 homodimer has a lower affinity and thermodynamic stability than the MST1 homodimer, while the monomer is slightly more stable. Our experimental results along with our theoretical considerations indicate that the SARAH domain is merely a dimerization domain and that the differences between the individual sequences lead to different stabilities and affinities that might have an important functional role.

PubMed: 23331050
DOI: 10.1021/BI3014642

Experimental method

X-RAY DIFFRACTION (1.69 Å)