Structural insights into the activation of somatostatin receptor 2 by cyclic SST analogues.

Bo Q, Yang F, Li Y, Meng X, Zhang H, Zhou Y, Ling S, Sun D, Lv P, Liu L, Shi P, Tian C

Cell discovery20 May 2022Cited by 35 (Europe PMC)

PMID35595746PMCIDPMC9122944DOI10.1038/s41421-022-00405-2PepBankPUB-35595746

Summary

The endogenous cyclic tetradecapeptide SST14 was reported to stimulate all five somatostatin receptors (SSTR1-5) for hormone release, neurotransmission, cell growth arrest and cancer suppression. Two SST14-derived short cyclic SST analogues (lanreotide or octreotide) with improved stability and longer lifetime were developed as drugs to preferentially activate SSTR2 and treat acromegalia and neuroendocrine tumors. Here, cryo-EM structures of the human SSTR2-Gi complex bound with SST14, octreotide or lanreotide were determined at resolutions of 2.85 Å, 2.97 Å, and 2.87 Å, respectively. Structural and functional analysis revealed that interactions between β-turn residues in SST analogues and transmembrane SSTR2 residues in the ligand-binding pocket are crucial for receptor binding and functional stimulation of the two SST14-derived cyclic octapeptides. Additionally, Q102^2.63, N276^6.55, and F294^7.35 could be responsible for the selectivity of lanreotide or octreotide for SSTR2 over SSTR1 or SSTR4. These results provide valuable insights into further rational development of SST analogue drugs targeting SSTR2.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

2 results from studies that gave the peptide. No result from this study comes from people.

01LabIn vitro (cell-free)Mechanism
In structural and functional analysis, β-turn interactions with SSTR2 transmembrane residues were crucial for lanreotide receptor binding and functional stimulation.
In plain wordsIn lab tests, interactions between lanreotide β-turn residues and receptor residues were crucial for receptor binding and stimulation.
Peptide
Lanreotide
Outcome
Not applicableReceptor binding and stimulation interactions
Study
humann: not reported in source
SSTR2-Gi complex
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
Dose not stated
Source sentences
Summary
Structural and functional analysis revealed that interactions between β-turn residues in SST analogues and transmembrane SSTR2 residues in the ligand-binding pocket are crucial for receptor binding and functional stimulation of the two SST14-derived cyclic octapeptides.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, cryo-EM structures of the human SSTR2-Gi complex bound with SST14, octreotide or lanreotide were determined at resolutions of 2.85 Å, 2.97 Å, and 2.87 Å, respectively.
Show in the study text Report a problemFND-3559574602
02LabIn vitro (cell-free)Mechanism
In laboratory analysis, Q102, N276, and F294 could explain lanreotide selectivity for SSTR2 over SSTR1 or SSTR4.
In plain wordsIn lab tests, specific receptor residues could explain lanreotide preference for SSTR2 over SSTR1 or SSTR4.
Peptide
Lanreotide
Outcome
Not applicableSSTR2 selectivity residues
Study
humann: not reported in source
SSTR2-Gi complex
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
Dose not stated
Source sentences
Summary
Additionally, Q102^2.63, N276^6.55, and F294^7.35 could be responsible for the selectivity of lanreotide or octreotide for SSTR2 over SSTR1 or SSTR4.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, cryo-EM structures of the human SSTR2-Gi complex bound with SST14, octreotide or lanreotide were determined at resolutions of 2.85 Å, 2.97 Å, and 2.87 Å, respectively.
Show in the study text Report a problemFND-3559574603

Studies that did not test the peptide alone1

In this study, Lanreotide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Lanreotide.

03LabNot a test of Lanreotide aloneIn vitro (cell-free)Mechanism
In laboratory analysis, the lanreotide-bound human SSTR2-Gi complex structure was determined at 2.87 Å resolution.
In plain wordsIn lab tests, researchers determined the lanreotide-bound human receptor complex structure at 2.87 Å resolution.
Peptide
Lanreotide
Outcome
Not applicableLanreotide-bound SSTR2-Gi structure resolution
Study
humann: not reported in source
SSTR2-Gi complex
Outcome group
Receptor activity and mechanism · Pharmacology
Source sentences
Summary
Here, cryo-EM structures of the human SSTR2-Gi complex bound with SST14, octreotide or lanreotide were determined at resolutions of 2.85 Å, 2.97 Å, and 2.87 Å, respectively.
In this study, Lanreotide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Lanreotide.
Show in the study text Report a problemFND-3559574601

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:36 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

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