|
|
|
|
| LEADER |
01000naa a22002652 4500 |
| 001 |
NLM309736250 |
| 003 |
DE-627 |
| 005 |
20231225134554.0 |
| 007 |
cr uuu---uuuuu |
| 008 |
231225s2020 xx |||||o 00| ||eng c |
| 024 |
7 |
|
|a 10.1021/acs.langmuir.0c00770
|2 doi
|
| 028 |
5 |
2 |
|a pubmed24n1032.xml
|
| 035 |
|
|
|a (DE-627)NLM309736250
|
| 035 |
|
|
|a (NLM)32390436
|
| 040 |
|
|
|a DE-627
|b ger
|c DE-627
|e rakwb
|
| 041 |
|
|
|a eng
|
| 100 |
1 |
|
|a Li, Lei
|e verfasserin
|4 aut
|
| 245 |
1 |
0 |
|a Characterization of the Spatial Organization of Raf Isoforms Interacting with K-Ras4B in the Lipid Membrane
|
| 264 |
|
1 |
|c 2020
|
| 336 |
|
|
|a Text
|b txt
|2 rdacontent
|
| 337 |
|
|
|a ƒaComputermedien
|b c
|2 rdamedia
|
| 338 |
|
|
|a ƒa Online-Ressource
|b cr
|2 rdacarrier
|
| 500 |
|
|
|a Date Completed 21.06.2021
|
| 500 |
|
|
|a Date Revised 21.06.2021
|
| 500 |
|
|
|a published: Print-Electronic
|
| 500 |
|
|
|a Citation Status MEDLINE
|
| 520 |
|
|
|a Activation of Raf kinases by the membrane-anchored protein K-Ras4B is a key step of cellular signal regulation. As a predominant variant of the Ras family, K-Ras4B has been considered to be a major drug target in cancer therapy. Therefore, an integrated study of Raf interaction with membrane-associated K-Ras4B is essential. While the Ras-binding domain (RBD) of Raf contains the main binding interface to K-Ras4B, its cysteine-rich domain (CRD) is thought to be responsible for its association with the membrane interface. We applied time-lapse tapping-mode atomic force microscopy to visualize and characterize the interaction of these binding motifs of A-, B-, and C-Raf isoforms with K-Ras4B in a raft-like anionic model biomembrane. However, we found that the RBDs of the Raf isomers are readily recruited to K-Ras4B nanoclusters in the lipid membrane, with different efficiencies. Unexpectedly and different from A-Raf-RBD, B- and C-Raf-RBD are able to bind markedly also directly to the lipid membrane. We also found that Raf-RBD-CRD is readily recruited to the K-Ras4B forming nanoclusters in the fluid membrane phase, with the CRD domains binding to the lipid interface. The K-Ras4B-nanoclusters are likely to enhance Raf binding and activate signaling by enriching the Raf proteins and facilitating formation of Raf dimers. Interestingly, A-, B-, and C-Raf-RBD-CRD are also able to bind directly to the heterogeneous membrane surrounding the K-Ras4B nanoclusters, which could potentially enhance the overall affinity to K-Ras4B in a Raf-isoform-dependent manner. Overall, these results provide new insights into the spatial organization of the membrane-associated Raf-Ras signaling module for the various Raf isoforms, which is important for understanding the activation of Raf kinases and required for the development of drugs against cancers through targeting Raf-Ras interactions
|
| 650 |
|
4 |
|a Journal Article
|
| 650 |
|
4 |
|a Research Support, Non-U.S. Gov't
|
| 650 |
|
7 |
|a Lipids
|2 NLM
|
| 650 |
|
7 |
|a Protein Isoforms
|2 NLM
|
| 700 |
1 |
|
|a Möbitz, Simone
|e verfasserin
|4 aut
|
| 700 |
1 |
|
|a Winter, Roland
|e verfasserin
|4 aut
|
| 773 |
0 |
8 |
|i Enthalten in
|t Langmuir : the ACS journal of surfaces and colloids
|d 1992
|g 36(2020), 21 vom: 02. Juni, Seite 5944-5953
|w (DE-627)NLM098181009
|x 1520-5827
|7 nnns
|
| 773 |
1 |
8 |
|g volume:36
|g year:2020
|g number:21
|g day:02
|g month:06
|g pages:5944-5953
|
| 856 |
4 |
0 |
|u http://dx.doi.org/10.1021/acs.langmuir.0c00770
|3 Volltext
|
| 912 |
|
|
|a GBV_USEFLAG_A
|
| 912 |
|
|
|a SYSFLAG_A
|
| 912 |
|
|
|a GBV_NLM
|
| 912 |
|
|
|a GBV_ILN_22
|
| 912 |
|
|
|a GBV_ILN_350
|
| 912 |
|
|
|a GBV_ILN_721
|
| 951 |
|
|
|a AR
|
| 952 |
|
|
|d 36
|j 2020
|e 21
|b 02
|c 06
|h 5944-5953
|