User:Natalia de Araujo./Sandbox 1

This is a default text for your page Natalia de Araujo./Sandbox 1. Click above on edit this page to modify. Be careful with the < and > signs.

You may include any references to papers as in: the use of JSmol in Proteopedia ^[1] or to the article describing Jmol ^[2] to the rescue.

The first structure, displayed on the left-hand side of the screen, corresponds to 4jon, the Crystal structure of CEP170's transcript variant beta, from Homo sapiens. 4jon is a 5 chain structure obtained by X-ray Crystallography [1] and represents the first 126 residues of CEP170's N-termini region.

The second structure available for CEP170 is , a predicted 3D model representing its full lenght (1-1584).

Here we are going to focus on the Q5SW79 model due to its full sequence, allowing us to highlight residues and regions important for the understanding of CEP170's functions and interactions.

Q5SW79 Confidence Model

Before getting started, it is important to have in mind that the majority of the Q5SW79 structure has very low confidence, meaning the model most probably does not represent the real protein structure.

However, it stills helps us to have a good idea of the whole protein.

See below the confidence model from UniProt:

CEP170 gene

The CEP170 gene (OMIM*613023[9]) spans over 131,369 bases at 1q43, contains 30 exons, and encodes the Centrosomal Protein of 170 kDa (CEP170)[10].

Bulk RNA-seq of CEP170 [11](average expression of the gene) shows that CEP170 is expressed in a variety of tissues.

CEP170 protein

CEP170 is a pericentriolar protein that associates with the mother-centriole during interphase and with the spindle apparatus during mitosis^[3], showing a dynamic behavior throughout the cell cycle.

CEP170 functions are going to be discussed in the next section.

Function

Microtubule organization

Microtubule nucleation

Protein-Protein Interactions

• CHEK1 and circCHEK1_246aa

Through Co-IP [12]and MS[13] CEP170 was identified as a putative interactor with CHEK1, further confirmed with Co-IP in cells overexpressing CHEK1 ^[4] CHEK and circCHEK1_246aa (isoform from a cRNA) phosphorylate the residue of CEP170, which results in chromosomal instability seen in multiple myeloid cells.

• PLK1

Through yeast two-hybrid screen CEP170 was identified as a putative interactor with PLK1, further confirmed with Reciprocal Co-IP in vivo. PLK1 phosphorylates the C-termini region () of CEP170. ^[5]

• KIF2B

Welburn and Cheeseman

• TBK1

Pillai

• CCDC68 and CCDC120

Huang

• CCDC61

Barenz

• WDR62

Qin

• Interacts with CCDC68 and CCDC120; leading to recruitment to centrosomes (PubMed:28422092).

Interacts with PLK1 (PubMed:15616186).

Interacts with NIN (By similarity).

Interacts with FHDC1 (By similarity).

Interacts with CCDC61 (PubMed:30354798, PubMed:31789463).

Interacts with TBK1; efficient complex formation may be dependent on the presence of CCDC61 (PubMed:30354798).

Structural highlights

As seen by Guarguaglini et al. (2005) all three splice variants harbor an N-terminal forkhead-associated (FHA) domain and a serine-rich domain and a short coiled-coil region in the C-terminal half.

The C-terminus region harbors 3 globular domains, [.......] located at and the second at

• Phosphorilation

As shown previously, CEP170 is a phosphoprotein, phosphorylated probably by PLK1, TBK1, CHEK1 and circCHEK1_246aa and [...] The serine-rich region is located at x-x, harboring around 48 phosphorylated residues

• FHA Domain: 23 – 73

FHA N-terminal (22-73aa) iso alfa

• Serine-rich region 968-1228aa iso alfa

• Targeting to microtubules: 853 – 1584

• Interaction with CCDC61: 1015 – 1460

• Targeting to centrosomes:1113 – 1584

• Coiled coil domain:1467 – 1495(mesmo da guargua, iso alfa).. Protein which contains at least one coiled coil domain, a type of secondary structure composed of two or more alpha helices which entwine to form a cable structure. In proteins, the helical cables serve a mechanical role in forming stiff bundles of fibres. uniprot https://www.uniprot.org/keywords/KW-0175

Disease

• • • https://proteopedia.org/wiki/index.php/Image:AF-Q5SW79-F1.pdb [imagem da proteina inteira]

This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.