Structural highlights
Disease
RASM_HUMAN Noonan syndrome. The disease is caused by variants affecting the gene represented in this entry.
Function
RASM_HUMAN Serves as an important signal transducer for a novel upstream stimuli in controlling cell proliferation. Activates the MAP kinase pathway.[1] [2]
Publication Abstract from PubMed
M-RAS plays a crucial role in the RAF-MEK signaling pathway. When activated by GTP, M-RAS forms a complex with SHOC2 and PP1C, initiating downstream RAF-MEK signal transduction. In this study, the crystal structure of the GDP-bound human M-RAS protein is presented with two forms of crystal packing. Both the full-length and truncated human M-RAS structures aligned well with the high-confidence section of the AlphaFold2-predicted structure with low r.m.s.d., except for the Switch regions. Despite high sequence similarity to the available mouse M-RAS structure, the full-length human M-RAS structure exhibits unique crystal packing. This inactive human M-RAS structure could offer novel insights for the design of selective compounds targeting M-RAS.
Crystal structure of the GDP-bound human M-RAS protein in two crystal forms.,Bester SM, Abrahamsen R, Rodrigues Samora L, Wu WI, Mou TC Acta Crystallogr F Struct Biol Commun. 2024 Sep 1;80(Pt 9):220-227. doi: , 10.1107/S2053230X24007969. Epub 2024 Aug 28. PMID:39196705[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rodriguez-Viciana P, Oses-Prieto J, Burlingame A, Fried M, McCormick F. A phosphatase holoenzyme comprised of Shoc2/Sur8 and the catalytic subunit of PP1 functions as an M-Ras effector to modulate Raf activity. Mol Cell. 2006 Apr 21;22(2):217-30. doi: 10.1016/j.molcel.2006.03.027. PMID:16630891 doi:http://dx.doi.org/10.1016/j.molcel.2006.03.027
- ↑ Higgins EM, Bos JM, Mason-Suares H, Tester DJ, Ackerman JP, MacRae CA, Sol-Church K, Gripp KW, Urrutia R, Ackerman MJ. Elucidation of MRAS-mediated Noonan syndrome with cardiac hypertrophy. JCI Insight. 2017 Mar 9;2(5):e91225. doi: 10.1172/jci.insight.91225. PMID:28289718 doi:http://dx.doi.org/10.1172/jci.insight.91225
- ↑ Bester SM, Abrahamsen R, Rodrigues Samora L, Wu WI, Mou TC. Crystal structure of the GDP-bound human M-RAS protein in two crystal forms. Acta Crystallogr F Struct Biol Commun. 2024 Sep 1;80(Pt 9):220-227. PMID:39196705 doi:10.1107/S2053230X24007969
