7n1o
From Proteopedia
The von Willebrand factor A domain of human capillary morphogenesis gene II, flexibly fused to the 1TEL crystallization chaperone
Structural highlights
DiseaseETV6_HUMAN Note=A chromosomal aberration involving ETV6 is found in a form of chronic myelomonocytic leukemia (CMML). Translocation t(5;12)(q33;p13) with PDGFRB. It is characterized by abnormal clonal myeloid proliferation and by progression to acute myelogenous leukemia (AML).[1] Note=Chromosomal aberrations involving ETV6 are found in a form of acute myeloid leukemia (AML). Translocation t(12;22)(p13;q11) with MN1; translocation t(4;12)(q12;p13) with CHIC2.[2] [3] [4] Note=Chromosomal aberrations involving ETV6 are found in childhood acute lymphoblastic leukemia (ALL). Translocations t(12;21)(p12;q22) and t(12;21)(p13;q22) with RUNX1/AML1. Note=A chromosomal aberration involving ETV6 is found in a form of pre-B acute myeloid leukemia. Translocation t(9;12)(p24;p13) with JAK2. Note=A chromosomal aberration involving ETV6 is found in myelodysplastic syndrome (MDS) with basophilia. Translocation t(5;12)(q31;p13) with ACSL6. Note=A chromosomal aberration involving ETV6 is found in acute eosinophilic leukemia (AEL). Translocation t(5;12)(q31;p13) with ACSL6. Note=A chromosomal aberration involving ETV6 is found in myelodysplastic syndrome (MDS). Translocation t(1;12)(p36.1;p13) with MDS2. Defects in ETV6 are a cause of myeloproliferative disorder chronic with eosinophilia (MPE) [MIM:131440. A hematologic disorder characterized by malignant eosinophils proliferation. Note=A chromosomal aberration involving ETV6 is found in many instances of myeloproliferative disorder chronic with eosinophilia. Translocation t(5;12) with PDGFRB on chromosome 5 creating an ETV6-PDGFRB fusion protein. Defects in ETV6 are a cause of acute myelogenous leukemia (AML) [MIM:601626. AML is a malignant disease in which hematopoietic precursors are arrested in an early stage of development.[5] [6] [7] Note=A chromosomal aberration involving ETV6 is found in acute lymphoblastic leukemia. Translocation t(9;12)(p13;p13) with PAX5.ANTR2_HUMAN Defects in ANTXR2 are the cause of infantile systemic hyalinosis (ISH) [MIM:236490. This autosomal recessive syndrome is similar to JHF, but has an earlier onset and a more severe course. Symptoms appear at birth or within the first months of life, with painful, swollen joint contractures, osteopenia, osteoporosis and livid red hyperpigmentation over bony prominences. Patients develop multiple subcutaneous skin tumors and gingival hypertrophy. Hyaline deposits in multiple organs, recurrent infections and intractable diarrhea often lead to death within the first 2 years of life. Surviving children may suffer from severely reduced mobility due to joint contractures.[8] [9] Defects in ANTXR2 are the cause of juvenile hyaline fibromatosis (JHF) [MIM:228600. JHF is an autosomal recessive syndrome that is similar to ISH but takes a milder course. It is characterized by hyaline deposition in the dermis, multiple subcutaneous skin tumors and gingival hypertrophy, followed by progressive joint contractions, osteopenia and osteoporosis that may lead to a severe limitation of mobility.[10] [11] FunctionETV6_HUMAN Transcriptional repressor; binds to the DNA sequence 5'-CCGGAAGT-3'.ANTR2_HUMAN Necessary for cellular interactions with laminin and the extracellular matrix.[12] [13] Publication Abstract from PubMedWhile conducting pilot studies into the usefulness of fusion to TELSAM polymers as a potential protein crystallization strategy, we observed novel properties in crystals of two TELSAM-target protein fusions, as follows. (i) A TELSAM-target protein fusion can crystallize more rapidly and with greater propensity than the same target protein alone. (ii) TELSAM-target protein fusions can be crystallized at low protein concentrations. This unprecedented observation suggests a route to crystallize proteins that can only be produced in microgram amounts. (iii) The TELSAM polymers themselves need not directly contact one another in the crystal lattice in order to form well-diffracting crystals. This novel observation is important because it suggests that TELSAM may be able to crystallize target proteins too large to allow direct inter-polymer contacts. (iv) Flexible TELSAM-target protein linkers can allow target proteins to find productive binding modes against the TELSAM polymer. (v) TELSAM polymers can adjust their helical rise to allow fused target proteins to make productive crystal contacts. (vi). Fusion to TELSAM polymers can stabilize weak inter-target protein crystal contacts. We report features of these TELSAM-target protein crystal structures and outline future work needed to validate TELSAM as a crystallization chaperone and determine best practices for its use. Crystals of TELSAM-target protein fusions that exhibit minimal crystal contacts and lack direct inter-TELSAM contacts.,Nawarathnage S, Soleimani S, Mathis MH, Bezzant BD, Ramirez DT, Gajjar P, Bunn DR, Stewart C, Smith T, Pedroza Romo MJ, Brown S, Doukov T, Moody JD Open Biol. 2022 Mar;12(3):210271. doi: 10.1098/rsob.210271. Epub 2022 Mar 2. PMID:35232248[14] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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