Elizeu/sandbox/citocromo c

From Proteopedia

Revision as of 12:07, 27 January 2017 by Julie Langlois (Talk | contribs)
Jump to: navigation, search

User: Julie Langlois/PsaA


NCBI Accession: P42363.1

Uniprot Accesion: POA4G2

PDB ID: 3ZK7


Contents

Overview

PsaA (Pneumococcal surface antigen A) is a high affinity substrate-binding lipoprotein [1] detected on all known serotypes of Streptococcus pneumoniae. It facilitates the acquisition of Mn2+ by being part of the cell's ABC (ATP binding complex) transporter and plays a major role in pneumococcal attachment to the host cell and virulence [2].

Streptococcus pneumonia, also widely known as pneumococcus, is a Gram positive coccus with a diameter of 0.5 to 1 μm. As a member of the genus Streptococcus it typically forms diplococci and can live both under aerobic or anaerobic conditions. In healthy carriers it resides in the nasopharynx [3]. However, the bacterium may become pathogenic in elderly and immunocompromised people as well as in children due to a weaker immune system. In fact, S. pneumoniae is the most frequent opportunistic pathogen worldwide and causes many types of diseases including otitis media, meningitis, sepsis and pneumonia [4]. The genome of S. pneumoniae is a closed, circular DNA structure that contains between 2.0 and 2.1 million base pairs [3].

Streptococcus pneumoniae
Streptococcus pneumoniae [5]















PsaA protein

Between the first to the 24th amino acid namely the red motif there is the signal peptide and the second one is the Pfam motif[6].






Zinc in excess has significant toxicity to bacteria because it is an important innate defense mechanism. There are many Zinc molecules in the human body. Manganese is important for the virulence, growth and proliferation of Streptococcus pneumoniae. Zinc could compete for Manganese binding. However Manganese has more affinity for PsaA than Zinc but Zinc is not transported by the ABC-transporter. Zinc competition reduces intracellular Manganese resulting in up-regulation of PsaBCA expression. [7]


Structure of ABC-transporter








ABC transporter

Bacterial ABC transporters are an important class of transmembrane transporters. They are involved in the import and export of a wide variety of substrates, including sugars, amino acids, peptides, polyamines, and cations. [9]They can be considered as a promising target for antimicrobial strategies. ABC transporter consists of four membrane-associated proteins with two ATP-binding proteins (ATPases) and two permeases. [10]


In the case of PsaA, the ABC transporter is composed of an ATP-binding protein (PsaB), an integral membrane protein (PsaC) and PsaA itself as a lipoprotein that possess a metal-ion binding site. This confers the protein to bind divalent metal-ions, however, with a preference for Mn2+ [11]. The genes that encode for the components of the ABC transport system are psaA, psaB and psaC, respectively. They are organized consecutively in the psaBCA operon, together with psaD, the gene encoding for a thiol peroxidase (see below). [12]. .

Psa operon
Psa operon [13]
Image:Linear structure PsaA.jpg
Linear structure of PsaA

Structure

The protein PsaA has a molecular weight of 34.538 kDa with 309 residues [14]. The overall size of the protein approximated from its crystal structure is 40 by 40 by 70 Å [15]. As a member of the Lipoprotein receptor-associated antigen I (LraI) family, the PsaA molecule contains four distinct regions. An N-terminal leader sequence of 20 amino acids holds an LxACy consensus sequence that is recognized and cleaved by signal peptidase II [15]. A lipid moiety (diacylglycerol [16]) is added to the cysteine residue and mediates the anchorage of the protein to the cytoplasmic membrane. Apart from this leader sequence, the rest of the protein consists of two twofold-pseudosymmetrical (β/α)4 sandwich domains, of which the β-strands of each domain form parallel β-sheets [16]. In total the two domains form two lobes connected via an α-helical linker which constitutes the solute-binding site [15].

Secondary structure of PsaA:

[1]

3D structure of PsaA in the metal-free, open state

Drag the structure with the mouse to rotate
Retrieved from "http://52.214.119.220/wiki/index.php/Elizeu/sandbox/citocromo_c"
Personal tools