PDBsum entry 2ma2

Calcium-binding protein

PDB id: 2ma2

Contents

Protein chain

81 a.a.

PDB id:

2ma2

Name:

Calcium-binding protein

Title:

Solution structure of rasgrp2 ef hands bound to calcium

Structure:

Ras guanyl-releasing protein 2. Chain: a. Synonym: calcium and dag-regulated guanine nucleotide exchange factor i, caldag-gefi, cdc25-like protein, hcdc25l, f25b3.3 kinase-like protein. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: rasgrp2, cdc25l, mcg7. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

10 models

Authors:

J.Kuriyan,J.Iwig,Y.Vercoulen,R.Das,T.Barros,A.Limnander,Y.Che, J.Pelton,D.Wemmer,J.Roose

Key ref:

J.S.Iwig et al. (2013). Structural analysis of autoinhibition in the Ras-specific exchange factor RasGRP1. Elife, 2, e00813. PubMed id: 23908768 DOI: 10.7554/eLife.00813

Date:

24-Jun-13 Release date: 21-Aug-13

Protein chain

Q7LDG7  (GRP2_HUMAN) -  RAS guanyl-releasing protein 2 from Homo sapiens

Seq: 609 a.a.

Struc: 81 a.a.

DOI no: 10.7554/eLife.00813

Elife 2:e00813 (2013)

PubMed id: 23908768

Structural analysis of autoinhibition in the Ras-specific exchange factor RasGRP1.

J.S.Iwig, Y.Vercoulen, R.Das, T.Barros, A.Limnander, Y.Che, J.G.Pelton, D.E.Wemmer, J.P.Roose, J.Kuriyan.

ABSTRACT

RasGRP1 and SOS are Ras-specific nucleotide exchange factors that have distinct roles in lymphocyte development. RasGRP1 is important in some cancers and autoimmune diseases but, in contrast to SOS, its regulatory mechanisms are poorly understood. Activating signals lead to the membrane recruitment of RasGRP1 and Ras engagement, but it is unclear how interactions between RasGRP1 and Ras are suppressed in the absence of such signals. We present a crystal structure of a fragment of RasGRP1 in which the Ras-binding site is blocked by an interdomain linker and the membrane-interaction surface of RasGRP1 is hidden within a dimerization interface that may be stabilized by the C-terminal oligomerization domain. NMR data demonstrate that calcium binding to the regulatory module generates substantial conformational changes that are incompatible with the inactive assembly. These features allow RasGRP1 to be maintained in an inactive state that is poised for activation by calcium and membrane-localization signals. DOI:http://dx.doi.org/10.7554/eLife.00813.001.