Sandbox Reserved 824
From Proteopedia
Line 60: | Line 60: | ||
<scene name='56/568022/Hsrp54m_dimer/1'>hSRP54M Dimer</scene> | <scene name='56/568022/Hsrp54m_dimer/1'>hSRP54M Dimer</scene> | ||
+ | <scene name='56/568022/Hsrp54m_h1_to_h7/1'>hSRP54M and its 7 alpha helixes</scene> |
Revision as of 14:21, 3 January 2014
|
This Sandbox is Reserved from 06/12/2018, through 30/06/2019 for use in the course "Structural Biology" taught by Bruno Kieffer at the University of Strasbourg, ESBS. This reservation includes Sandbox Reserved 1480 through Sandbox Reserved 1543. |
To get started:
More help: Help:Editing |
Contents |
Context / Work in Progress
SRP54 is a 54kDa cytosolic protein part of the Signal Recognition Particle (SRP). SRP54 homologous proteins can be referred to as Ffh (Fifty Four Homologous)*.
SRP is a ribonucleoprotein particle essential for the translation and integration in membranes of signal peptide-bearing proteins. SRP is composed of an RNA backbone, on which bind different proteins.
For example Mammalian SRP are formed of the RNA 7S and SRN 9-14-19-54-68-72*.
SRP54 and regions of RNA 7S are highly conserved in every organism and it was found that these two components are sufficient to form a minimal SRP*.
The role of SRP is to :
- Bind signal peptide bearing proteins at the beginning of their translation by the ribosome (at this step we call the ribosome and the protein it began to translate the Ribosome Nascent Chain – RNC)
- Stop protein elongation
- Dock the RNC to a SRP Receptor (SR) and insert the protein into a translocon channel. This final step is GTP-dependant.
SRP54 is responsible for the signal peptide binding and the GTP-dependant interaction with SR. This protein is therefore essential in the SRP mechanism resulting in the integration of proteins into membranes or their secretion.
asterisque = references aux publis, faire le lien avec les publis cites en fin d’article
Structure
(Domaines N, G, M / Interaction N-G => Domaine NG pour activité GTPase / Mention du domaine NG très similaire de SR alpha Domaine M avec partie rigide en c-term, partie flexible en n-term et grossièrement leurs fonctions)
SRP54 is composed of 3 domains: N terminal domain with 4 alpha-helices; G domain, central, corresponding to a GTPase activity and the M domain (Methionin Rich). M domain corresponds to 1qb2 protein.
SRP54M is composed by 504 Amino Acids, forming 7 alpha helices (h1 to h7). The helices 2 to 7 from the core protein, stabilized by hydrophobic residues such as Met382 (invariant) and by hydrogen and salt bonds involving conserved amino acids: Glu386, Arg402, and Arg405. The helix 1 extends from the core protein.
The protein was difficult to crystalize, and it appears in the crystals dimeres of 1QB2 protein. 1QB2 contains 2 binding domains:
- Peptide signal binding domain
- SRP RNA binding domain
- Signal peptide binding domain
This domain involves h2 to h4 to generate the hydrophobic groove witch will recognise and bind the nascent protein. It also involves a highly structured loop between h2 and h3: 17 amino acids (349 to 365) with the Met-Ile-Pro-Gly motif (351 to 354) and two phenylalanins (355 and 359). In addition of the loop and the three helices, h1 is located near the hydrophobic groove and is an equivalent of the signal peptide. This similarity explains the dimerization of 1QB2 in the crystal. Each h1 take place in the groove of the opposite monomer. Because of this interaction, we are able to suppose that h1 in vivo is involved in protection of the hydrophobic groove against solvents.
- SRP RNA binding domain
The RNA is linked to the 1QB2 protein by electrostatic potential. This interaction involves helices 5 and 6, but also some small parts of helices 4 and 7. This proposal is confirmed by experiments of directed site mutation (Gowda et al., 1998). It appears that some basics residues are required (Arg402 and Arg405) to maintain the core structure and the interaction with the RNA.
Remarks:
It is important to note the linkage between M and G subunits of SRP54, GTP hydrolysis in the G subunit could provide conformational changes and modify interactions, especially for electrostatic bonds with the signal peptide (released after hydrolysis).
Fonctions
Lien avec la structure, explications des intéractions en fonction des structures etc ...