#37413

[grouchydairy]

jisoo kim

#lucy dot jpg #jisoo kim #37413

[iahaber]

İA HABER AJANSI Maltepe’de 4 aracın karıştığı kazada, 4 kişi yaralandı https://bbcturk.com/maltepede-4-aracin-karistigi-kazada-4-kisi-yaralandi/37413/?utm_source=dlvr.it&utm_medium=tumblr www.bbcturk.com https://iahaber.com

#Gündem

[takhfifekhob]

شلوار اسلش دو رنگ خط دار اسپرت Y-3 مدل 37413

شلوار اسلش دو رنگ خط دار اسپرت Y-3 مدل 37413 💰 قیمت 179 تومان 🚛 پرداخت درب منزل 🛍️ برای خرید به لینک زیر مراجعه کنید 👇 🛒 : https://www.takhfifekhob.com/213745

[jobrxiv]

Research Associate in Cell Culture at Sania Therapeutics Sania Rx Ltd Join #Sania as a #research associate and help revolutionise treatments for neurological diseases See the full job description on jobRxiv: https://jobrxiv.org/job/sania-rx-ltd-27778-research-associate-in-cell-culture-at-sania-therapeutics/?feed_id=37413 #ScienceJobs #hiring #research London #UnitedKingdomUK #ResearchAssistant #Researcher #Scientist

[pdfsayar]

Birol Öztürk Ahmet Kaya

Birol Öztürk Ahmet Kaya

1 sonuç Boyut Önizleme İndirme HÂkimler Ve Savcılar Kurulu Birinci Dairesinin …S.No Sicil No Adı ve Soyadı Bulunduğu Görev Atandığı Görev 144 37413 Ali ÇOBAN Bursa Cumhuriyet Savcısı İstanbul Cumhuriyet Savcılığı 145 37460 Esra Nesibe ŞAHİN TUNCAY Ankara Bölge Adliye Mahkemesi Üyesi Ankara Bölge Adliye Mahkemesi Daire BaşkanlığıKaynak:…

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[lifesciencepotluck]

Figuring out structure

Proteins are like molecular machines. Unlike actual machines, proteins can fold into intricate 3-D structures on their own. Wouldn't it be convenient if your bookshelf from IKEA could do that? If we want to understand how proteins work, we need a blueprint. Some parts of the protein are essential for stability; other parts are crucial for getting things done through binding or catalysis. We need to understand how different parts of the protein fit together; this is where Structural Biology comes in. Getting the 3-D structure is one of the main steps in characterising new anemone toxins. I will cover some of the techniques we use to investigate the toxin structure.

The hierarchy of protein structure goes like this: primary structure-->secondary structure-->tertiary structure-->quaternary structure. For anemone toxins, we don't have to worry about the quaternary structure. Usually, anemone toxins have one polypeptide, not multiple polypeptides.

Figure 1. Structures of anemone toxins (Source: Norton, R. S, 2009)

Primary structure:

It's the amino acid sequence or 'code' for the protein. You can get the amino acid sequence from DNA, mRNA or protein sequencing. Protein sequencing just gives you the sequence for your protein. However, if we use DNA or mRNA sequencing, then we have to figure out the 'mature' peptide sequence. DNA and mRNA code for the 'first draft' of the peptide. After translating mRNA to protein, the signal peptide and pro-peptide are attached to the 'mature peptide.' Those two parts of the protein get cut out before our mature peptide can go out in the world and decimate prey.

Secondary structure:

Our flat polypeptide chain will fold into different secondary structures like alpha-helices, beta-sheets, beta turns, etc. Circular dichroism and Fourier transform infrared radiation (FT-IR) can tell us about the secondary structure of the toxin. CD and FT-IR are commonly used to predict the amount of each secondary structure in proteins. For CD, we measure how much of circularly polarised light in the far-UV region is absorbed by the sample. We use curve fitting programs to determine which combination of secondary structures fits the spectra the best (e.g. 50% beta-sheet, 10% alpha-helix, 20 % random coil and 20 % beta-turn). FT-IR works similarly, but we use infrared radiation instead of polarised light. FT-IR is a better option for investigating the interactions between pore-forming toxins and lipid membranes. The lipid vesicle or 'sacs' scatter polarised light, which it makes challenging to use CD for the same purpose.

One of the best things about spectroscopic techniques is that they are not as time-consuming as, X-ray crystallography. You can have multiple CD, and FT-IR runs in 1-2 hours and get the processed data before lunch. However, CD and FT-IR are low-resolution techniques. They don't tell you the exact position and orientation of tryptophan 32. We need atomic resolution structures to get an in-depth understanding of how anemone toxins work.

Tertiary structure:

The full 3-D structure of proteins will have secondary structure plus the disulphide linkages, salt bridges, hydrophobic interactions. There are two main ways of getting atomic resolution structures: X-ray crystallography and NMR. X-ray crystallography can give high-resolution 3-D structures—if you manage to please the crystal gods. If you don't have the ideal crystallisation conditions—no crystal for you. I know PhD students who spent 12-18 months on crystallising their protein. However, once you get past the crystallisation bottleneck, the diffraction experiments and data processing doesn't take as much time. In theory, you can get better resolution with X-ray crystallography than NMR. Let's assume you don't have time for crystallisation and you go with NMR. NMR is excellent for finding the structure of smaller proteins, but for larger proteins, you have to use isotopic labelling. Some proteins that are too big for NMR. In X-ray crystallography, the protein is a 'frozen' state. However, NMR also lets you study proteins in solution to understand the dynamics of the protein. You can observe how the protein changes when it binds to something.

We can also predict the 3-D structure of the toxin-based on the sequence alone.

How?

Computer magic !

With the protein data bank and structure prediction tools like SWISS-MODEL, you can predict the 3-D structure of a new toxin. If there is an anemone toxin in the database with an experimentally determined 3-D structure and it has high sequence similarity with your new toxin, you can use homolog modelling. If you can't use homology modelling, you can use de novo structure prediction like I-TASSER. In de novo modelling, the program predicts the structure for smaller sections of the protein and uses those bits to build the full predicted model. Model prediction isn't 100% accurate, and we still have to determine the 3-D structure experimentally. However, predicted 3-D structures act as a guide.

Every technique has its strengths and weaknesses. A good researcher tries to use the most suitable method for their project to its full potential. You have to realise the power that's inside.

So, what can you do once you have the 3-D structure of a toxin?

I am going to use APETx1 from the clonal anemone as an example. APETx1 is a potassium channel toxin, which targets the Ether-a-gogo channels in heart cells. Since APETx1 is a small potassium channel toxin, Chagot and company could use NMR. They found that APETx1 belong to the Defensin family. A variety of anti-bacterial proteins and ion channel toxins belong to this family. Proteins with Defensin-4 domain, have double or triple-stranded antiparallel b-sheets linked to a short a-helix by two disulphide bridges. Since NMR can reveal disulphide linkages, Chagot found APETx1 has an inhibitor cysteine knot (ICK). The inhibitor cysteine is a very popular protein fold because it's so stable that it makes proteins resilient against heat stress and proteolysis. Getting the structure of a toxin allows us to classify the toxin and compare it with structurally similar toxins. Since APETx1 has structurally similarity with two other toxins BeKm1 and CnErg1, you can infer it would have a similar mechanism for blocking potassium channels. Chagot suggested that five key amino acids on APETx1 (i.e. Tyr 5, Tyr 32, Phe33, Lys8 and Lys 18) 'block' the Ether-a-gogo channels through electrostatic interactions.

Figure 2. 3-D structure for APETx1 (Source: Chagot et al, 2005)

In short, we can use a variety of biophysical techniques to get structural information for new toxins  and the structure provides insight into the function. Protein structure and function are different sides of the same coin. Next time, I will flip the coin by covering how we figure out function.

Citations:

Chagot, B., Diochot, S., Pimentel, C., Lazdunski, M. & Darbon, H. Solution structure of APETx1 from the sea anemone Anthopleura elegantissima: A new fold for an HERG toxin. Proteins Struct. Funct. Genet. 59, 380–386 (2005).

Jouiaei, M. et al. Ancient venom systems: A review on cnidaria toxins. Toxins (Basel). 7, 2251–2271 (2015).

Norton, R. S. Structures of sea anemone toxins. Toxicon 54, 1075–1088 (2009).

Norton, R. S. & Pallaghy, P. K. The cystine knot structure of ion channel toxins and related polypeptides. Toxicon 36, 1573–1583 (1998).

Dauplais, M. et al. On the Convergent Evolution of Animal Toxins. J. Biol. Chem. 272, 4302–4309 (1997).

Belmonte, G. et al. Primary and secondary structure of a pore-forming toxin from the sea anemone, Actinia equina L., and its association with lipid vesicles. BBA - Biomembr. 1192, 197–204 (1994).

Honma, T. & Shiomi, K. Review Article Peptide Toxins in Sea Anemones: Structural and Functional Aspects. Mar. Biotechnol. 8, 1–10 (2006).

Bernard Gilquin, Judith Racape, Anja Wrisch, Violeta Visan, Alain Lecoq, Stephan Grissmer, Andre´Menez, and S. G. Structure of the BgK-Kv1.1 Complex based on distance restraints identified by double mutant cycles: Molecular basis for convergent evolution of Kv1 channel blockers. J. Biol. Chem. 277, 37406–37413 (2002).

#anemone toxins #Anemone toxins 201 #Structural Biology #sea anemone #Protein Science #bioinformatics

[imagination-483]

~ Have you watched the "Switch" presentation yet? 😄💕 Really looking forward to the new Zelda game 😍😅 ~ 👇🏻Products used👇🏻 •Base coat from @trindcosmetics •Glitter from @bornprettystore •Stamping plate ID #37413 , polish and liquid latex from @bornprettystore •"Good to go" from @essienordics

#37413

[danskjavlarna]

Source details and larger version.

My modest collection of vintage hobby horses galloping along.

#hobby horse #mask #jousting #vintage illustration

[cbschrock]

Bandana Mani

Did you see my post last night on IG?? Well, as promised, I will review the plate I used for my paisley mani.

Plate L020 from Harunouta https://www.bornprettystore.com/rectangle-stamping-plate-paisley-bandanna-pattern-nail-plate-harunouta-https://www.bornprettystore.com/rectangle-stamping-plate-paisley-bandanna-pattern-nail-plate-harunouta-l020-p-37413.html37413.html is a Paisley filled wonderland. There are large and small patterns, as well as a "buffet" area for those of us that have a large or long nail. The images are etched well and pick up with silicon or clear stampers (I used this stamper(https://www.bornprettystore.com/rose-gold-nail-stamper-chess-clear-jelly-silicone-head-with-born-pretty-scraper-p-39258.html).

My base colors are Nauticaly Navy and Cadillac Red from Color Club.

If you use CSKW10 at Born Pretty, you will receive a 10% discount.

#mani #notd #hospitalhands #nailpolish

#naildesign #nailpornography #nailart #nails #nailpolish #notd #manicures #mani #manicure

[zarkachat]

وزارة الصحة السورية تعلن اليوم الخميس عن تسجيل 53 إصابة جديدة بفيروس كورونا 

 أعلنت وزارة الصحة السورية اليوم (الخميس 27 كانون الثاني 2022) عن تسجيل 53 إصابة جديدة بفيروس كورونا المستجد في البلاد.  وأشارت وزارة الصحة إلى أن عدد الإصابات المسجلة في سوريا حتى الآن بلغ 51177 حالة بينها 10785 حالة نشطة. كما لفتت إلى شفاء 310 حالات من الإصابات المسجلة بفيروس كورونا ليرتفع عدد المتعافين من الفيروس إلى 37413. وأعلنت الوزارة عن 2 حالات وفاة من الإصابات المسجلة بمرض كوفيد 19…

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#أخبار السعودية #كورونا السعودية

[interestingasfuckreddit]

Falling in love by accident !!! https://t.me/InterestingasfuckBackup/37413 #interestingasfuck #rinterestingasfuck #interestingasfuckreddit #interestingasfucksubreddit #r_interestingasfuck

#interestingasfuck #rinterestingasfuck #interestingasfuckreddit #interestingasfucksubreddit #r_intere

[iamprotech]

Craftsman - CMXZVBE37413 CRAFTSMAN 37413 2-1/2 in. Dusting Brush Wet/Dry Vac Attachment, Black

Craftsman – CMXZVBE37413 CRAFTSMAN 37413 2-1/2 in. Dusting Brush Wet/Dry Vac Attachment, Black

Price: (as of – Details) Wood chips, dust, metal shavings and other stubborn debris won’t stand a chance against the CRAFTSMAN 2-1/2 in. Dusting Brush. Drag it around your shop, deep clean your car, or dust your blinds – this shop vacuum accessory is ideal for detail cleaning most hard and intricate surfaces. Fits most CRAFTSMAN and other brands’ wet/dry vacs with a 2-1/2 in. hose…

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#Parts and Accessories

[ranzwarcom]

The absolute beginner’s guide to film photography: 7 common camera types

https://www.ranzware.com/37413

[metwallybendary]

بوابة النجوم .. حددت اللائحة التنفيذية لقانون تنظيم ممارسة العمل الأهلى الصادر برقم 149 لسنة 2019، خطوات توفيق أوضاع الجمعيات والمؤسسات الأهلية والاتحادات المقيدة لدى الوحدة المصدر:اليوم السابع تعرف على خطوات توفيق أوضاع الجمعيات والمؤسسات الأهلية وفقا للقانون...

#دوري أبطال إفريقيا #أخبار الأهلي #أخبار الزمالك #موعد مباراة ليفربول #موعد مباراة برشلونة #موعد

[imagination-483]

~ All the reviews have been posted ✨💕 Thank you to each and everyone of you who've been following me so far 🙈💕💕 ~ Stamping plate from @bornprettystore ID #37413 💕

#37413