Abstract:
:Rasal is a modular multi-domain protein of the GTPase-activating protein 1 (GAP1) family; its four known members, GAP1m, Rasal, GAP1IP4BP and Capri, have a Ras GTPase-activating domain (RasGAP). This domain supports the intrinsically slow GTPase activity of Ras by actively participating in the catalytic reaction. In the case of Rasal, GAP1IP4BP and Capri, their remaining domains are responsible for converting the RasGAP domains into dual Ras- and Rap-GAPs, via an incompletely understood mechanism. Although Rap proteins are small GTPase homologues of Ras, their catalytic residues are distinct, which reinforces the importance of determining the structure of full-length GAP1 family proteins. To date, these proteins have not been crystallized, and their size is not adequate for nuclear magnetic resonance (NMR) or for high-resolution cryo-electron microscopy (cryoEM). Here we present the low resolution structure of full-length Rasal, obtained by negative staining electron microscopy, which allows us to propose a model of its domain topology. These results help to understand the role of the different domains in controlling the dual GAP activity of GAP1 family proteins.
journal_name
Biol Chemjournal_title
Biological chemistryauthors
Cuellar J,Valpuesta JM,Wittinghofer A,Sot Bdoi
10.1515/hsz-2017-0159subject
Has Abstractpub_date
2017-12-20 00:00:00pages
63-72issue
1eissn
1431-6730issn
1437-4315pii
/j/bchm.just-accepted/hsz-2017-0159/hsz-2017-0159.journal_volume
399pub_type
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