Multiple-choice questions (MCQs) on Titin

Multiple-choice questions (MCQs) on Titin

Here’s a clean, editable table with 20 key points about Titin in heart failure:

No.	Point
1	Titin is a giant sarcomeric protein essential for myocardial elasticity and structure.
2	It spans half of the sarcomere, connecting the Z-disk to the M-line.
3	Titin contributes significantly to passive tension and diastolic function in the heart.
4	Mutations in the TTN gene are a major genetic cause of dilated cardiomyopathy (DCM).
5	TTN truncating variants (TTNtv) lead to impaired Titin function and contribute to HF.
6	In heart failure, altered Titin stiffness affects myocardial compliance and filling.
7	Titin isoform switching (N2BA to N2B) alters cardiac muscle elasticity in disease.
8	Increased expression of the stiffer N2B isoform is common in failing hearts.
9	Post-translational modifications (e.g., phosphorylation) regulate Titin elasticity.
10	Protein kinase A (PKA) phosphorylation reduces Titin stiffness, improving compliance.
11	Protein kinase G (PKG) also phosphorylates Titin and modulates diastolic function.
12	Reduced PKG activity in HF leads to Titin hypophosphorylation and increased stiffness.
13	Titin degradation by proteases can exacerbate cardiac dysfunction in HF.
14	Titin interacts with other proteins to coordinate mechanotransduction in cardiomyocytes.
15	Titin kinase domain mutations affect signal transduction linked to cardiac remodeling.
16	Titin-based passive tension influences ventricular filling pressures and compliance.
17	Therapeutic strategies targeting Titin phosphorylation are under investigation.
18	Biomarkers related to Titin fragments are explored for heart failure diagnosis.
19	Titin mutations can lead to both systolic and diastolic heart failure phenotypes.
20	Research on Titin’s role is critical for understanding and treating HF with preserved EF.

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1. Titin is known as the largest protein in the human body. Which structural feature primarily contributes to its enormous size?
A) High number of alpha-helices in its structure
B) Multiple immunoglobulin-like and fibronectin type III domains arranged in series
C) Extensive glycosylation on its surface
D) Presence of many disulfide bridges forming loops

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Answer: B) Multiple immunoglobulin-like and fibronectin type III domains arranged in series

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Explanation: Titin’s gigantic size is due to the repetition of many modular domains, mainly immunoglobulin (Ig)-like and fibronectin type III (FNIII)-like domains arranged in tandem along its length, enabling it to span half of the sarcomere.

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2. Which region of titin is primarily responsible for its elastic properties in muscle?
A) Z-disc region
B) A-band region
C) I-band region
D) M-line region

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Answer: C) I-band region

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Explanation: The I-band region of titin contains extensible segments such as the PEVK domain and serially linked Ig domains, which unfold and refold during muscle stretching and relaxation, conferring elastic properties.

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3. Titin plays a crucial role in sarcomere assembly and signaling. Which of the following proteins directly interacts with titin to mediate signaling pathways?
A) Nebulin
B) Muscle LIM protein (MLP)
C) Actin
D) Myosin light chain kinase (MLCK)

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Answer: B) Muscle LIM protein (MLP)

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Explanation: Muscle LIM protein (MLP) interacts with the titin kinase domain and participates in mechanosensing and signaling pathways important for muscle gene expression and hypertrophy.

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4. Mutations in the titin gene (TTN) are most commonly associated with which of the following diseases?
A) Duchenne muscular dystrophy
B) Hypertrophic cardiomyopathy
C) Becker muscular dystrophy
D) Myasthenia gravis

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Answer: B) Hypertrophic cardiomyopathy

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Explanation: TTN mutations are frequently linked to cardiomyopathies, especially dilated and hypertrophic cardiomyopathy, due to titin’s structural and signaling roles in cardiac muscle.

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5. During muscle contraction, titin’s role includes:
A) Hydrolyzing ATP to generate force
B) Serving as a molecular scaffold that maintains sarcomere integrity
C) Initiating calcium release from the sarcoplasmic reticulum
D) Directly binding to tropomyosin to regulate thin filament activation

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Answer: B) Serving as a molecular scaffold that maintains sarcomere integrity

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Explanation: Titin acts as a giant scaffold protein that stabilizes the sarcomere by linking the Z-disc to the M-line and maintaining the alignment of thick and thin filaments.

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6. Which enzymatic activity is associated with the titin protein?
A) ATPase activity
B) Kinase activity
C) Phosphatase activity
D) Protease activity

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Answer: B) Kinase activity

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Explanation: The titin molecule contains a C-terminal kinase domain near the M-line, which plays a role in mechanotransduction and muscle signaling.

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7. Which domain of titin is primarily responsible for its binding to thick filaments (myosin)?
A) Z-disc domain
B) A-band domain
C) I-band domain
D) M-line domain

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Answer: B) A-band domain

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Explanation: The A-band region of titin interacts with myosin thick filaments, anchoring titin to the thick filament lattice within the sarcomere.

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Here are advanced multiple-choice questions (MCQs) on Titin, covering its structure, function, and role in muscle physiology and related research:

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Advanced MCQs on Titin

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1. Which of the following best describes the function of Titin in sarcomere structure?

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A. It facilitates calcium binding for contraction
B. It transmits force between actin filaments
C. It acts as a molecular spring, maintaining passive elasticity
D. It binds ATP to power muscle contraction

✅ Correct answer: C. It acts as a molecular spring, maintaining passive elasticity

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2. The N-terminal of the Titin molecule is anchored in which region of the sarcomere?

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A. M-line
B. A-band
C. I-band
D. Z-disk

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✅ Correct answer: D. Z-disk

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3. Titin spans from the Z-disk to which structure in the sarcomere?

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A. M-line
B. H-zone
C. I-band
D. A-band

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✅ Correct answer: A. M-line

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4. Titin is encoded by which gene in humans?

A. ACTN1
B. MYH7
C. TTN
D. TNNT2

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✅ Correct answer: C. TTN

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5. Mutations in the TTN gene are most commonly associated with which cardiac condition?

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A. Hypertrophic cardiomyopathy
B. Dilated cardiomyopathy
C. Restrictive cardiomyopathy
D. Arrhythmogenic right ventricular cardiomyopathy

✅ Correct answer: B. Dilated cardiomyopathy

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6. Which domain of Titin contributes most significantly to its elasticity?

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A. Ig-like domains
B. Fibronectin III domains
C. PEVK domain
D. Kinase domain

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✅ Correct answer: C. PEVK domain

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7. Which of the following techniques is commonly used to study the mechanical properties of Titin at the single-molecule level?

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A. Western blotting
B. Cryo-electron microscopy
C. Optical tweezers
D. SDS-PAGE

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✅ Correct answer: C. Optical tweezers

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8. The kinase domain of Titin is thought to play a role in:

A. ATP hydrolysis during contraction
B. Phosphorylation-dependent signal transduction
C. Regulation of calcium levels
D. Sarcoplasmic reticulum formation

✅ Correct answer: B. Phosphorylation-dependent signal transduction

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9. In skeletal muscle, the expression of different Titin isoforms affects:

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A. The rate of action potential conduction
B. The length-tension relationship and passive stiffness
C. The level of troponin-tropomyosin complex activity
D. Myosin ATPase activity

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✅ Correct answer: B. The length-tension relationship and passive stiffness

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10. The extensible region of Titin is primarily located in which part of the sarcomere?

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A. A-band
B. Z-line
C. M-line
D. I-band

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✅ Correct answer: D. I-band

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1. Which of the following best describes the function of Titin in sarcomere structure?

A. It facilitates calcium binding for contraction
B. It transmits force between actin filaments
C. ✅ It acts as a molecular spring, maintaining passive elasticity
D. It binds ATP to power muscle contraction

Explanation- Titin acts as a molecular spring and contributes to passive elasticity in muscle fibers. It resists overstretching and helps return the sarcomere to its resting length after contraction.

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2. The N-terminal of the Titin molecule is anchored in which region of the sarcomere?

A. M-line
B. A-band
C. I-band
D. ✅ Z-disk

Explanation- Titin anchors at the Z-disk with its N-terminal and spans across the I-band and A-band, terminating at the M-line. This structure stabilizes the sarcomere during contraction and stretching.

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3. Titin spans from the Z-disk to which structure in the sarcomere?

A. ✅ M-line
B. H-zone
C. I-band
D. A-band

Explanation- Titin is the largest known protein and spans half the length of the sarcomere—from the Z-disk to the M-line—providing structural integrity and elasticity.

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4. Titin is encoded by which gene in humans?

A. ACTN1
B. MYH7
C. ✅ TTN
D. TNNT2

Explanation

The TTN gene encodes Titin. It is one of the largest genes in the human genome, and mutations here are implicated in various myopathies and cardiomyopathies.

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5. Mutations in the TTN gene are most commonly associated with which cardiac condition?

A. Hypertrophic cardiomyopathy
B. ✅ Dilated cardiomyopathy
C. Restrictive cardiomyopathy
D. Arrhythmogenic right ventricular cardiomyopathy

Explanation

TTN truncating variants (TTNtv) are the most common genetic cause of **dilated cardiomyopathy (DCM)**, leading to weakened heart muscle and chamber dilation.

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6. Which domain of Titin contributes most significantly to its elasticity?

A. Ig-like domains
B. Fibronectin III domains
C. ✅ PEVK domain
D. Kinase domain

Explanation

The **PEVK domain**, rich in Proline (P), Glutamate (E), Valine (V), and Lysine (K), is highly extensible and accounts for much of Titin’s elastic properties in the I-band region.

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7. Which of the following techniques is commonly used to study the mechanical properties of Titin at the single-molecule level?

A. Western blotting
B. Cryo-electron microscopy
C. ✅ Optical tweezers
D. SDS-PAGE

Explanation

**Optical tweezers** allow scientists to apply and measure minute forces on single molecules, making them ideal for probing the elasticity and mechanical unfolding of Titin domains.

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8. The kinase domain of Titin is thought to play a role in:

A. ATP hydrolysis during contraction
B. ✅ Phosphorylation-dependent signal transduction
C. Regulation of calcium levels
D. Sarcoplasmic reticulum formation

Explanation

Titin’s kinase domain can act as a **mechanosensor**, participating in **signal transduction pathways** related to muscle gene expression and hypertrophic responses.

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9. In skeletal muscle, the expression of different Titin isoforms affects:

A. The rate of action potential conduction
B. ✅ The length-tension relationship and passive stiffness
C. The level of troponin-tropomyosin complex activity
D. Myosin ATPase activity

Explanation

Different **Titin isoforms** (longer or shorter) affect the **compliance** of muscle fibers, influencing how stiff or elastic a muscle is during passive stretch.

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10. The extensible region of Titin is primarily located in which part of the sarcomere?

A. A-band
B. Z-line
C. M-line
D. ✅ I-band

Explanation

The extensible portion of Titin resides mainly in the **I-band**, where it behaves like a spring during muscle stretching, contributing to the sarcomere’s passive tension.

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It looks like you meant TTN mutation rather than “TIN mutation,” as TIN is not commonly referenced in muscle or cardiac genetics. Here’s a clear explanation about TTN mutations:

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What is a TTN Mutation?

• TTN gene encodes Titin, the largest known human protein, essential for muscle elasticity and sarcomere structure.
• A TTN mutation refers to a change or alteration in the DNA sequence of the TTN gene.
• These mutations can be:
  • Truncating mutations (TTNtv): These cause premature stop codons, leading to a shortened, usually nonfunctional Titin protein.
  • Missense mutations: Change a single amino acid but may have variable effects.
• Clinical relevance:
  • TTN mutations are the most common genetic cause of dilated cardiomyopathy (DCM).
  • They may also contribute to other cardiac diseases like hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy, and arrhythmias.
• Pathophysiology: TTN mutations often impair Titin’s ability to maintain sarcomere integrity and passive tension, leading to cardiac dysfunction.

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Here’s a concise list of Titin-related diseases with brief descriptions

Disease	Description
Dilated Cardiomyopathy (DCM)	Most common genetic cause linked to TTN truncating mutations; characterized by ventricular dilation and systolic dysfunction.
Hypertrophic Cardiomyopathy (HCM)	Some mutations in TTN are associated with HCM, leading to thickened ventricular walls.
Restrictive Cardiomyopathy (RCM)	Rare TTN mutations can cause RCM, leading to stiff ventricular walls and impaired filling.
Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)	Some overlap with TTN mutations affecting cardiac structure and rhythm.
Familial Heart Failure	TTN mutations cause inherited forms of heart failure with variable phenotypes.
Muscular Dystrophies	Certain TTN mutations linked to skeletal muscle disorders like tibial muscular dystrophy.
Congenital Myopathies	Rare TTN mutations can lead to congenital muscle weakness and structural abnormalities.
Early-Onset Atrial Fibrillation	TTN variants have been implicated in increased risk of atrial arrhythmias.