Details of the PSS

General Information of Protein Scaffold of SBP (PSS) (ID: PS042)
PSS Name	Knottin
Synonyms	Cystine knot; Cystine knot miniprotein; Inhibitor cystine knot peptide; Microbody; ICK
Diagrammatic Sketch
Highest Status	Research
Class	Non-Antibody
Fold Type	Beta-Sheets + Loops
Thermal Denaturation TEMP	>80℃
Sequence Length	25-60
Molecular Weight	3-6 kDa

Parental Protein of This PSS

Parental Protein Name	Synonym	PDB ID	UniProt ID	Origin
Agatoxin	AgTx	2N6N	Q5Y4U5	Spider
Agouti-related protein	AgRP	1HYK	O00253	Human
Cellulose-binding domain	CBD	1CX1	P14090	Fungus Trichoderma reesei
Chlorotoxin	CTX	5L1C	P45639	Scorpion
Ecballium elaterium trypsin inhibitor II	EETI-II	2ETI	P12071	Cucumis sativus; Squash plant Ecballium elaterium
Kalata B1	Kalata-B1	1JJZ	P56254	Oldenlandia affinis
Momordica cochinchinensis trypsin inhibitor	MCoTI-I/II	1IB9	P82409	Momordica cochinchinensis; Synthetic construct
Spinacia oleracea trypsin inhibitor	SOTI	4AOR	P84779	Spinach seeds

Synthetic Binding Protein (SBP) Featuring this PSS

SBP Name	Highest Status	Template	Expression System	Selection Method	Details	Ref
Knottin anti-CTLA-4 MC-CT-010	Research	oMCoTI-	Escherichia coli	Yeast display	SBP Info	[1]
Knottin anti-CTLA-4 MC-CT-020	Research	oMCoTI-	Escherichia coli	Yeast display	SBP Info	[1]
Knottin anti-CTLA-4 MC-CT-030	Research	oMCoTI-	Escherichia coli	Yeast display	SBP Info	[1]
Knottin anti-CTLA-4 MC-CT-040	Research	oMCoTI-	Escherichia coli	Yeast display	SBP Info	[1]
Knottin anti-FXIIa cMCoFx1	Research	N.A.	N.A.	mRNA display	SBP Info	[2]
Knottin anti-FXIIa cMCoTI-fxL1	Research	N.A.	N.A.	mRNA display	SBP Info	[2]
Knottin anti-FXIIa cMCoTI-fxL5	Research	N.A.	N.A.	mRNA display	SBP Info	[2]
Knottin anti-Integrin 2bA	Research	AgRP	Pichia pastoris GS115	Yeast display	SBP Info	[3]
Knottin anti-Integrin 2bJ	Research	AgRP	Pichia pastoris GS115	Yeast display	SBP Info	[3]
Knottin anti-Integrin 2bO	Research	AgRP	Pichia pastoris GS115	Yeast display	SBP Info	[3]
Knottin anti-Integrin 6C	Research	AgRP	Pichia pastoris	Yeast display	SBP Info	[4]
Knottin anti-Integrin 7A	Research	AgRP	Pichia pastoris	Yeast display	SBP Info	[4]
Knottin anti-Integrin 7C	Research	AgTx	Pichia pastoris	Yeast display	SBP Info	[4]
Knottin anti-Integrin 7E	Research	AgRP	Pichia pastoris	Yeast display	SBP Info	[4]
Knottin anti-Integrin 7J	Research	AgRP	Pichia pastoris	Yeast display	SBP Info	[4]
Knottin anti-Integrin b3A	Research	AgRP	Pichia pastoris GS115	Yeast display	SBP Info	[3]
Knottin anti-Integrin b3I	Research	AgRP	Pichia pastoris GS115	Yeast display	SBP Info	[3]
Knottin anti-Integrin EETI-1.5B	Research	EETI-II	Saccharomyces cerevisiae	Yeast display	SBP Info	[5]
Knottin anti-Integrin EETI-2.5D	Research	EETI-II	Saccharomyces cerevisiae	Yeast display	SBP Info	[5]
Knottin anti-Integrin EETI-2.5F	Research	EETI-II	Saccharomyces cerevisiae	Yeast display	SBP Info	[5]
Knottin anti-nAChR Ms11a-1	Research	N.A.	Escherichia coli BL21 (DE3)	N.A.	SBP Info	[6]
Knottin anti-nAChR Ms11a-2	Research	N.A.	Escherichia coli BL21 (DE3)	N.A.	SBP Info	[6]
Knottin anti-nAChR Ms11a-3	Research	N.A.	Escherichia coli BL21 (DE3)	N.A.	SBP Info	[6]
Knottin anti-nAChR Ms11a-4	Research	N.A.	Escherichia coli BL21 (DE3)	N.A.	SBP Info	[6]
Knottin MCoLib	Research	N.A.	N.A.	N.A.	SBP Info	[7]
Knottin anti-c-Mpl AGTP-3	Research	AgRP	Escherichia coli	N.A.	SBP Info	[8]
Knottin anti-c-Mpl AGTP-4	Research	AgRP	Escherichia coli	N.A.	SBP Info	[8]
Knottin anti-c-Mpl AGTP-5	Research	AgRP	Escherichia coli	N.A.	SBP Info	[8]
Knottin anti-c-Mpl ETTP-2	Research	EETI-II	Escherichia coli	N.A.	SBP Info	[8]
Knottin anti-c-Mpl ETTP-3	Research	EETI-II	Escherichia coli	N.A.	SBP Info	[8]
Knottin anti-Integrin R(O)1	Research	N.A.	Saccharomyces cerevisiae EBY100	Yeast display	SBP Info	[9]
Knottin anti-Integrin R(O)2	Research	N.A.	Saccharomyces cerevisiae EBY100	Yeast display	SBP Info	[9]
Knottin anti-Integrin R(O)3	Research	N.A.	Saccharomyces cerevisiae EBY100	Yeast display	SBP Info	[9]
Knottin anti-Integrin S(O)1	Research	N.A.	Saccharomyces cerevisiae EBY100	Yeast display	SBP Info	[9]
Knottin anti-Integrin S(O)2	Research	N.A.	Saccharomyces cerevisiae EBY100	Yeast display	SBP Info	[9]
Knottin anti-Integrin S(O)3	Research	N.A.	Saccharomyces cerevisiae EBY100	Yeast display	SBP Info	[9]
Knottin anti-Matriptase-1 MCoTI Var. 1	Research	MCoTI-	N.A.	Yeast display	SBP Info	[10]
Knottin anti-Matriptase-1 MCoTI Var. 2	Research	MCoTI-	N.A.	Yeast display	SBP Info	[10]
Knottin anti-Matriptase-1 MCoTI Var. 3	Research	MCoTI-	N.A.	Yeast display	SBP Info	[10]
Knottin anti-Matriptase-1 MCoTI Var. 4	Research	MCoTI-	N.A.	Yeast display	SBP Info	[10]
Knottin anti-Matriptase-1 SOTI Var. 1	Research	SOTI-	N.A.	Yeast display	SBP Info	[10]
Knottin anti-NRP1 N2.1	Research	Kalata B1	N.A.	Bacteria display	SBP Info	[11]
Knottin anti-NRP1 N2.2	Research	Kalata B1	N.A.	Bacteria display	SBP Info	[11]
Knottin anti-NRP1 N2.6	Research	Kalata B1	N.A.	Bacteria display	SBP Info	[11]
Knottin anti-Integrin AgTx 7C	Research	AgTx	N.A.	N.A.	SBP Info	[12]
Knottin anti-Integrin AgTx 7C(R21)	Research	AgTx	N.A.	N.A.	SBP Info	[12]
Knottin anti-Mast cell tryptase beta oMCoEETI(KKV)	Research	MCoEETI-II	N.A.	N.A.	SBP Info	[13]

References

1	Cystine-knot peptides targeting cancer-relevant human cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). J Pept Sci. 2015 Aug;21(8):651-60.
2	An Ultrapotent and Selective Cyclic Peptide Inhibitor of Human -Factor XIIa in a Cyclotide Scaffold. J Am Chem Soc. 2021 Nov 10;143(44):18481-18489.
3	Cystine-knot peptides engineered with specificities for (IIb)(3) or (IIb)(3) and (v)(3) integrins are potent inhibitors of platelet aggregation. J Mol Recognit. Jan-Feb 2011;24(1):127-35.
4	Engineered cystine-knot peptides that bind alpha(v)beta(3) integrin with antibody-like affinities. J Mol Biol. 2009 Jan 30;385(4):1064-75.
5	Engineered cystine knot peptides that bind alphavbeta3, alphavbeta5, and alpha5beta1 integrins with low-nanomolar affinity. Proteins. 2009 Nov 1;77(2):359-69.
6	Peptides from the Sea Anemone Metridium senile with Modified Inhibitor Cystine Knot (ICK) Fold Inhibit Nicotinic Acetylcholine Receptors. Toxins (Basel). 2022 Dec 30;15(1):28.
7	Cystine Knot Peptides with Tuneable Activity and Mechanism. Angew Chem Int Ed Engl. 2022 May 2;61(19):e202200951.
8	Grafting of thrombopoietin-mimetic peptides into cystine knot miniproteins yields high-affinity thrombopoietin antagonists and agonists. FEBS J. 2007 Jan;274(1):86-95.
9	Pharmacokinetically stabilized cystine knot peptides that bind alpha-v-beta-6 integrin with single-digit nanomolar affinities for detection of pancreatic cancer. Clin Cancer Res. 2012 Feb 1;18(3):839-49.
10	Combinatorial optimization of cystine-knot peptides towards high-affinity inhibitors of human matriptase-1. PLoS One. 2013 Oct 11;8(10):e76956.
11	Design of a cyclotide antagonist of neuropilin-1 and -2 that potently inhibits endothelial cell migration. ACS Chem Biol. 2013;8(6):1147-54.
12	Engineering agatoxin, a cystine-knot peptide from spider venom, as a molecular probe for in vivo tumor imaging. PLoS One. 2013;8(4):e60498.
13	Engineered cystine knot miniproteins as potent inhibitors of human mast cell tryptase beta. J Mol Biol. 2010 Jan 8;395(1):167-75.