PDBsum entry 3mjh

Protein transport

PDB id: 3mjh

Contents

Protein chains

168 a.a. *

34 a.a. *

33 a.a. *

Ligands

GTP ×2

Metals

_MG ×2

_ZN ×2

Waters ×312

* Residue conservation analysis

PDB id:

3mjh

Name:

Protein transport

Title:

Crystal structure of human rab5a in complex with the c2h2 zinc finger of eea1

Structure:

Ras-related protein rab-5a. Chain: a, c. Fragment: residues 16-183. Engineered: yes. Early endosome antigen 1. Chain: b, d. Fragment: c2h2-type, residues 36-69. Synonym: endosome-associated protein p162, zinc finger fyve domain- containing protein 2.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: rab5, rab5a. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: early endosomal antigen1(eea1), eea1, zfyve2.

Resolution:

2.03Å R-factor: 0.196 R-free: 0.260

Authors:

A.K.Mishra,S.Eathiraj,D.G.Lambright

Key ref:

A.Mishra et al. (2010). Structural basis for Rab GTPase recognition and endosome tethering by the C2H2 zinc finger of Early Endosomal Autoantigen 1 (EEA1). Proc Natl Acad Sci U S A, 107, 10866-10871. PubMed id: 20534488

Date:

12-Apr-10 Release date: 05-May-10

Protein chains

P20339  (RAB5A_HUMAN) -  Ras-related protein Rab-5A from Homo sapiens

Seq: 215 a.a.

Struc: 168 a.a.*

Protein chain

Q15075  (EEA1_HUMAN) -  Early endosome antigen 1 from Homo sapiens

Seq: 1411 a.a.

Struc: 34 a.a.

Protein chain

Q15075  (EEA1_HUMAN) -  Early endosome antigen 1 from Homo sapiens

Seq: 1411 a.a.

Struc: 33 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 1: Chains A, C: E.C.3.6.5.2 - small monomeric GTPase.
• Reaction: GTP + H2O = GDP + phosphate + H⁺

GTP (Bound ligand (Het Group name = GTP) corresponds exactly) + H2O = GDP + phosphate + H(+)

• Enzyme class 2: Chains B, D: E.C.?

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Proc Natl Acad Sci U S A 107:10866-10871 (2010)

PubMed id: 20534488

Structural basis for Rab GTPase recognition and endosome tethering by the C2H2 zinc finger of Early Endosomal Autoantigen 1 (EEA1).

A.Mishra, S.Eathiraj, S.Corvera, D.G.Lambright.

ABSTRACT

Regulation of endosomal trafficking by Rab GTPases depends on selective interactions with multivalent effectors, including EEA1 and Rabenosyn-5, which facilitate endosome tethering, sorting, and fusion. Both EEA1 and Rabenosyn-5 contain a distinctive N-terminal C(2)H(2) zinc finger that binds Rab5. How these C(2)H(2) zinc fingers recognize Rab GTPases remains unknown. Here, we report the crystal structure of Rab5A in complex with the EEA1 C(2)H(2) zinc finger. The binding interface involves all elements of the zinc finger as well as a short N-terminal extension but is restricted to the switch and interswitch regions of Rab5. High selectivity for Rab5 and, to a lesser extent Rab22, is observed in quantitative profiles of binding to Rab family GTPases. Although critical determinants are identified in both switch regions, Rab4-to-Rab5 conversion-of-specificity mutants reveal an essential requirement for additional substitutions in the proximal protein core that are predicted to indirectly influence recognition through affects on the structure and conformational stability of the switch regions.