Humanin: Molecular Structure

Molecular Structure#

Humanin is a 24-amino acid peptide with the sequence MAPRGFSCLLLLTSEIDLPVKRRA, encoded by a short open reading frame within the mitochondrial 16S ribosomal RNA gene (MT-RNR2). The peptide has a molecular weight of approximately 2687.3 Da and the molecular formula C119H204N34O33S2.

In solution, humanin adopts a partially alpha-helical conformation, with the central hydrophobic segment (residues 9-15, CLLLLTS) forming a helix that is critical for membrane association and secretion.

Amino Acid Sequence#

Key Analogs#

S14G-Humanin (HNG)#

The most important humanin analog is S14G-humanin (HNG), in which serine at position 14 is replaced with glycine. This single amino acid substitution increases neuroprotective potency approximately 1000-fold. HNG is the standard form used in most preclinical research.

Other Analogs#

Structure-activity studies have identified several critical residues:

• Positions 3 and 19 (Pro): Important for biological activity
• Position 8 (Cys): C8A substitution abolishes activity
• Position 14 (Ser): S14G substitution dramatically enhances potency
• C-terminal residues: Required for receptor binding and neuroprotection

Pharmacokinetic Properties#

Native humanin has a very short circulating half-life due to rapid proteolytic degradation, which has driven the development of more stable analogs like HNG. Despite its short half-life, humanin produces sustained biological effects through activation of long-lasting intracellular signaling cascades.

Stability Characteristics#

Humanin is relatively unstable in biological fluids due to its peptide nature. Research preparations are typically lyophilized and stored at -20 to -80 degrees C. Reconstituted solutions should be used promptly or aliquoted and frozen to prevent degradation. The cysteine residue at position 8 can form disulfide bonds, contributing to dimerization and affecting biological activity.

Molecular Context#

Humanin belongs to the Anti-Aging category of research peptides. The molecular properties of Humanin determine its pharmacological behavior, including receptor binding, distribution, metabolism, and elimination. Understanding these properties is fundamental to interpreting clinical data and designing research protocols.

Structural Overview#

Humanin is characterized as: Humanin is a 24-amino acid peptide encoded by the MT-RNR2 gene within mitochondrial 16S ribosomal RNA. It adopts a partially helical structure in solution. Key structural features include a central hydrophobic domain (residues 9-15) required for membrane interaction and secretion, and a C-terminal domain important for receptor binding and neuroprotective activity..

Amino Acid Sequence Details#

The amino acid sequence of Humanin is: MAPRGFSCLLLLTSEIDLPVKRRA. This sequence determines the peptide's three-dimensional structure, receptor binding properties, and biological activity.

Pharmacokinetic Profile#

Half-Life: Minutes (native); improved with analogs

The half-life of a peptide influences dosing frequency, duration of effect, and the clinical utility of the compound. Researchers should consider the half-life when designing experimental protocols.

Related Reading#

• Humanin overview and research guide
• Peptides similar to Humanin
• Humanin research evidence