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Ebook Bioinformatics – Trends and methodologies: Part 2

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Nội dung chi tiết: Ebook Bioinformatics – Trends and methodologies: Part 2

Ebook Bioinformatics – Trends and methodologies: Part 2

Part 5Protein structure Analysis14A Bioinformatical Approach to study the Endosomal Sorting Complex Required for Transport (ESCRT) Machinery in Protoz

Ebook Bioinformatics – Trends and methodologies: Part 2zoan Parasites: The Entamoeba histolytica CaseIsrael Lopez-Reyes1, Cecilia Banuelos1, Abigail Betanzos2 and Esther Orozco2'3 Unstituto lie Cieiiciil I

f Teciioỉogín del Distrito Federal, 2Centrơ de IitvestignciÓH If de Estudios Avanzados del Institute Poỉitécnico Nnciounỉ, :'Lbiiversidnd Autóiioiua d Ebook Bioinformatics – Trends and methodologies: Part 2

e ìn Ciudad de Mexico, México1. Introduction1.1The potential of bioinformatics for the study of protein structure and functionProteins are macromolecu

Ebook Bioinformatics – Trends and methodologies: Part 2

les formed by amino acid polymers that regulate cellular functions. Each protein is composed by the repetition and combination of 20 different amino a

Part 5Protein structure Analysis14A Bioinformatical Approach to study the Endosomal Sorting Complex Required for Transport (ESCRT) Machinery in Protoz

Ebook Bioinformatics – Trends and methodologies: Part 2ons, determined by non-covalent interactions such as hydrogen bonding, ionic interactions, Van der Waals forces and hydrophobic packing, and covalent

interactions, such as disulfide bonds (Chiang et al., 2007).Determining the structure and function of a protein is a milestone of many aspects of mode Ebook Bioinformatics – Trends and methodologies: Part 2

rn biology to understand its role in cell physiology. Bioinformatics is the research, development or application of computational approaches for expan

Ebook Bioinformatics – Trends and methodologies: Part 2

ding the use of biological, medical, behavioral or health-related data. It also includes those tools to acquire, store, organize, archive, analyze or

Part 5Protein structure Analysis14A Bioinformatical Approach to study the Endosomal Sorting Complex Required for Transport (ESCRT) Machinery in Protoz

Ebook Bioinformatics – Trends and methodologies: Part 2nformatical tools have revealed the existence of protein "interactomes", demonstrating the interaction among distinct biomolecules (protein-protein, p

rotem-lipids, protem-carbohydrates, etc.) to perform cellular processes (Kuchaiev & Przulj, 2011).During the last decades, genome sequencing projects Ebook Bioinformatics – Trends and methodologies: Part 2

together with bioinformatics programs and algorithms have enormously contributed to understand protein structure, protein interactions and protein fun

Ebook Bioinformatics – Trends and methodologies: Part 2

ctions. At present, over six million unique protein sequences have been deposited in public databases, and this number is increasing rapidly. Meanwhil

Part 5Protein structure Analysis14A Bioinformatical Approach to study the Endosomal Sorting Complex Required for Transport (ESCRT) Machinery in Protoz

Ebook Bioinformatics – Trends and methodologies: Part 2elley & Sterberg, 2009). The greatest challenge the molecular biology community is facing today is to analyze the wealth of data that has been produce

d by the genome sequencing projects, where bioinformatics290 Bioinformatics - Trends and Methodologieshas been fundamental. Traditionally, molecular b Ebook Bioinformatics – Trends and methodologies: Part 2

iology research has been carried out entirely at the laboratory bench, but the huge increase in the amount of data has made necessary to incorporate c

Ebook Bioinformatics – Trends and methodologies: Part 2

omputers and sophisticated software into research.Additionally, availability of genome databases for distinct organisms has improved our knowledge on

Part 5Protein structure Analysis14A Bioinformatical Approach to study the Endosomal Sorting Complex Required for Transport (ESCRT) Machinery in Protoz

Ebook Bioinformatics – Trends and methodologies: Part 2asingly important approach for studying the numbers, locations, biochemical functions and evolution of genes and pro Lems.In this review, we selected

a particular scientific case to emphasize the usefulness and potential of bioinformatics in addressing a biological problem.Most cellular processes us Ebook Bioinformatics – Trends and methodologies: Part 2

e scaffold proteins to recruit other proteins and to facilitate their correct interaction and functioning. Thus, we focused on the very little studied

Ebook Bioinformatics – Trends and methodologies: Part 2

scaffold proteins that form die Endosomal Sorting Complexes Required for Transport (ESCRT) machinery during protozoan endex-ytosis, a fundamental pro

Part 5Protein structure Analysis14A Bioinformatical Approach to study the Endosomal Sorting Complex Required for Transport (ESCRT) Machinery in Protoz

Ebook Bioinformatics – Trends and methodologies: Part 2brt histolylicfl, as determined by the use of bioinformaticaI tools.1.2Role of the ESCRT in endocytosisEndocytosis is a crucial process in multiple ce

llular and physiological events, including nutrient uptake, virus budding, cell surface receptor downregulation and cell signaling. It involves the in Ebook Bioinformatics – Trends and methodologies: Part 2

ternalization of molecules or particles of different sizes from the external environment, through membrane remodeling and vesicle formation events (de

Ebook Bioinformatics – Trends and methodologies: Part 2

Souza et al., 2009). In endocytosis, a huge number of mteractomes are involved. In the study of the highly complex endocytosis process, bioinformatic

Part 5Protein structure Analysis14A Bioinformatical Approach to study the Endosomal Sorting Complex Required for Transport (ESCRT) Machinery in Protoz

Ebook Bioinformatics – Trends and methodologies: Part 2 and transport them along the endocytic pathway. Depending on their function, membrane proteins are recycled back to the cell surface or degraded at l

ysosomal compartments together with cargo. Delivery of endocytosed cargo for degradation occurs through the fusion of intracellular vesicles called ea Ebook Bioinformatics – Trends and methodologies: Part 2

rly and late endosomes that finally reach lysosomes.In the majority of cell types, late endosomes fuse among them to form multi vesicular bodies (MVB)

Ebook Bioinformatics – Trends and methodologies: Part 2

, which arc essential intermediates for nutrient, ligand and receptor trafficking (V\ illiams ít Urbé, 2007). rhe best characterized signal for enteri

Part 5Protein structure Analysis14A Bioinformatical Approach to study the Endosomal Sorting Complex Required for Transport (ESCRT) Machinery in Protoz

Ebook Bioinformatics – Trends and methodologies: Part 2 protein called ubiquitin, is covalently attached for cargo labeling. Most of the cargo proteins that accumulate in MVB are marked by a single ubiquit

in, which is recognized by' a specific and conserved protein machinery termed "Endosomal Sorting Complex Required for Transport (ESCRT)" and whose fun Ebook Bioinformatics – Trends and methodologies: Part 2

ction is fundamental during endocytosis (Williams it Urbé, 2007).The ESCRT machinery was first characterized in yeast. Il consists of a group of vacuo

Ebook Bioinformatics – Trends and methodologies: Part 2

lar protein sorting factors (some of them called Vps), which form different mullimeric complexes (ESCRT-0, -I, -II and -III) that bind among them but

Part 5Protein structure Analysis14A Bioinformatical Approach to study the Endosomal Sorting Complex Required for Transport (ESCRT) Machinery in Protoz

Ebook Bioinformatics – Trends and methodologies: Part 2ticai Approach to Study the Endosomal Sorting Complex Required forTransport (ESCRT) Machinery In Protozoan Parasites The Entamoeba Histolytica Case 29

1Fig. 1. The ESCRT machinery involved in the endosomal MVB pathway.292 Bioinformatics - Trends and Methodologies(A) Eukaryotic cells internalize cargo Ebook Bioinformatics – Trends and methodologies: Part 2

molecules from the external environment by endocytic processes. These molecules transit along several compartments for surface recycling or degradati

Ebook Bioinformatics – Trends and methodologies: Part 2

on. The degradation pathway involves an endomembrane system constituted of membrane bound organelles called endosomes that mature from early to late e

Part 5Protein structure Analysis14A Bioinformatical Approach to study the Endosomal Sorting Complex Required for Transport (ESCRT) Machinery in Protoz

Ebook Bioinformatics – Trends and methodologies: Part 2 pathway should be tagged with ubiquitin. In yeast, ubiquitination of cargo proteins is mediated by the ubiquitin ligase Rsp5 and by Bull. Then, the E

SCRT-0 complex initiates the MVB sorting process by endosomal membrane binding through the Vps27 domain, and ubiquitin recognition of cargo by UIM dom Ebook Bioinformatics – Trends and methodologies: Part 2

ains present in Vps27 and Hsel proteins. Subsequently, Vps27 activates the ESCRT-I complex through its interaction with Vps23. Ubiquitinated cargo IS

Ebook Bioinformatics – Trends and methodologies: Part 2

recognized by ESCRT-I (via the UEV domain of Vps23) and by ESCRT-II (via the NZF domain of Vps36). Vps36 has an extensive positively charged region wi

Part 5Protein structure Analysis14A Bioinformatical Approach to study the Endosomal Sorting Complex Required for Transport (ESCRT) Machinery in Protoz

Ebook Bioinformatics – Trends and methodologies: Part 2T-III also associates to accessor}’ proteins such as Brol and Doa4. Importantly, the Vps4 ATPase catalyzes the dissociation of ESCRT complexes to init

iate new cycles of cargo sorting and transport. Together, ESCRT-0 to -III and -accessor}’ proteins direct cargo sorting, vesicle fusion, and MVB bioge Ebook Bioinformatics – Trends and methodologies: Part 2

nesis (modified from Hurley

Ebook Bioinformatics – Trends and methodologies: Part 2

the MVB pathway initiates with the association of Vps27 and Hsel proteins to make up the ESCRT-0 complex. Vps27 has a FYVE (Fabl, YOTB, Vacl, EE Al)

Part 5Protein structure Analysis14A Bioinformatical Approach to study the Endosomal Sorting Complex Required for Transport (ESCRT) Machinery in Protoz

Ebook Bioinformatics – Trends and methodologies: Part 2election of ubiquitinated cargo at the endosomal membrane (Hurley Emr, 2006; Williams & Urbé, 2007). Then, ESCRT-0 recruits ESCRT-I, formed by Vps23,

Vps28, \’ps37 and Mvbl2 proteins (Curtiss et al., 2007; Katzmann et al., 2001). Vps23 also recognizes and binds ubiquitinated proteins through its ter Ebook Bioinformatics – Trends and methodologies: Part 2

minal UEV (Ubiquitin E2 Variant) domain. ESCRT-I binds to ESCRT-I1 formed by Vps22, Vps25 and Vps36 proteins (Babst et al., 2002a). This later protein

Ebook Bioinformatics – Trends and methodologies: Part 2

also displays an ubiquitm-interactmg domain and a recognition region for phosphoinositides binding. Next, ESCRT-II binds to the ESCRT-III complex com

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