1AA9

HUMAN C-HA-RAS(1-171)(DOT)GDP, NMR, MINIMIZED AVERAGE STRUCTURE


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 30 
  • Conformers Submitted: 
  • Selection Criteria: MINIMIZED AVERAGE STRUCTURE 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Regional polysterism in the GTP-bound form of the human c-Ha-Ras protein.

Ito, Y.Yamasaki, K.Iwahara, J.Terada, T.Kamiya, A.Shirouzu, M.Muto, Y.Kawai, G.Yokoyama, S.Laue, E.D.Walchli, M.Shibata, T.Nishimura, S.Miyazawa, T.

(1997) Biochemistry 36: 9109-9119

  • DOI: https://doi.org/10.1021/bi970296u
  • Primary Citation of Related Structures:  
    1AA9

  • PubMed Abstract: 

    The backbone 1H, 13C, and 15N resonances of the c-Ha-Ras protein [a truncated version consisting of residues 1-171, Ras(1-171)] bound with GMPPNP (a slowly hydrolyzable analogue of GTP) were assigned and compared with those of the GDP-bound Ras(1-171). The backbone amide resonances of amino acid residues 10-13, 21, 31-39, 57-64, and 71 of Ras(1-171).GMPPNP, but not those of Ras(1-171).GDP, were extremely broadened, whereas other residues of Ras(1-171).GMPPNP exhibited amide resonances nearly as sharp as those of Ras(1-171). GDP. The residues exhibiting the extreme broadening, except for residues 21 and 71, are localized in three functional loop regions [loops L1, L2 (switch I), and L4 (switch II)], which are involved in hydrolysis of GTP and interactions with other proteins. From the temperature and magnetic field strength dependencies of the backbone amide resonance intensities, the extreme broadening was ascribed to the exchange at an intermediate rate on the NMR time scale. It was shown that the Ras(1-171) protein bound with GTP or GTPgammaS (another slowly hydrolyzable analogue of GTP) exhibits the same type of broadening. Therefore, it is a characteristic feature of the GTP-bound form of Ras that the L1, L2, and L4 loop regions, but not other regions, are in a rather slow interconversion between two or more stable conformers. This phenomenon, termed a "regional polysterism", of these loop regions may be related with their multifunctionality: the GTP-dependent interactions with several downstream target groups such as the Raf and RalGDS families and also with the GTPase activating protein (GAP) family. In fact, the binding of Ras(1-171).GMPPNP with the Ras-binding domain (residues 51-131) of c-Raf-1 was shown to eliminate the regional polysterism nearly completely. It was indicated, therefore, that each target/regulator selects its appropriate conformer among those presented by the "polysteric" binding interface of Ras. As the downstream target groups exhibit no apparent sequence homology to each other, it is possible that one target group prefers a conformer different from that preferred by another group. The involvement of loop L1 in the regional polysterism might suggest that the negative regulators, GAPs, bind to the polysteric binding interface (loops L2 and L4) of Ras and cooperatively select a conformer suitable for transition of the GTPase catalytic center, involving loops L1 and L4, into the highly active state.


  • Organizational Affiliation

    Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
C-HA-RAS171Homo sapiensMutation(s): 0 
Gene Names: HUMAN C-HA-RAS GENE
UniProt & NIH Common Fund Data Resources
Find proteins for P01112 (Homo sapiens)
Explore P01112 
Go to UniProtKB:  P01112
PHAROS:  P01112
GTEx:  ENSG00000174775 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01112
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GDP
Query on GDP

Download Ideal Coordinates CCD File 
C [auth A]GUANOSINE-5'-DIPHOSPHATE
C10 H15 N5 O11 P2
QGWNDRXFNXRZMB-UUOKFMHZSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
B [auth A]MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 30 
  • Conformers Submitted: 
  • Selection Criteria: MINIMIZED AVERAGE STRUCTURE 

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 1997-07-29
    Type: Initial release
  • Version 1.1: 2008-03-24
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2022-02-16
    Changes: Data collection, Database references, Derived calculations, Other