Crystal Structure of Human P32, a Doughnut-shaped Acidic Mitochondrial Matrix Protein

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1999 Mar 31

PMID 10097078

Citations 118

Authors

J Jiang

Y Zhang

A R Krainer

R M Xu

Affiliations

Soon will be listed here.

Abstract

Human p32 (also known as SF2-associated p32, p32/TAP, and gC1qR) is a conserved eukaryotic protein that localizes predominantly in the mitochondrial matrix. It is thought to be involved in mitochondrial oxidative phosphorylation and in nucleus-mitochondrion interactions. We report the crystal structure of p32 determined at 2.25 A resolution. The structure reveals that p32 adopts a novel fold with seven consecutive antiparallel beta-strands flanked by one N-terminal and two C-terminal alpha-helices. Three monomers form a doughnut-shaped quaternary structure with an unusually asymmetric charge distribution on the surface. The implications of the structure on previously proposed functions of p32 are discussed and new specific functional properties are suggested.

Citing Articles

Mettl15-Mettl17 modulates the transition from early to late pre-mitoribosome.

Zgadzay Y, Mirabello C, Wanes G, Panek T, Chauhan P, Nystedt B bioRxiv. 2025; .

PMID: 39896671 PMC: 11785013. DOI: 10.1101/2024.12.18.629302.

A new peptide inhibitor of C1QBP exhibits potent anti-tumour activity against triple negative breast cancer by impairing mitochondrial function and suppressing homologous recombination repair.

Li X, Wu Y, Zhang M, Wang F, Yin H, Zhang Y Clin Transl Med. 2025; 15(1):e70162.

PMID: 39748215 PMC: 11695203. DOI: 10.1002/ctm2.70162.

The mitochondrial long non-coding RNA lncMtloop regulates mitochondrial transcription and suppresses Alzheimer's disease.

Xiong W, Xu K, Sun J, Liu S, Zhao B, Shi J EMBO J. 2024; 43(23):6001-6031.

PMID: 39424953 PMC: 11612450. DOI: 10.1038/s44318-024-00270-7.

Endogenous complement 1q binding protein (C1qbp) regulates mitochondrial permeability transition and post-myocardial infarction remodeling and dysfunction.

Gutierrez-Aguilar M, Klutho P, Aguayo-Ortiz R, Song L, Baines C J Mol Cell Cardiol. 2024; 196:1-11.

PMID: 39209214 PMC: 11534557. DOI: 10.1016/j.yjmcc.2024.08.005.

Double-Edged Sword: Exploring the Mitochondria-Complement Bidirectional Connection in Cellular Response and Disease.

Lin J, Hwang S, Luo H, Mohamud Y Biology (Basel). 2024; 13(6).

PMID: 38927311 PMC: 11200454. DOI: 10.3390/biology13060431.

References

Neupert W . Protein import into mitochondria. Annu Rev Biochem. 1997; 66:863-917. DOI: 10.1146/annurev.biochem.66.1.863. View

Wang S, Trumble W, Liao H, Wesson C, Dunker A, Kang C . Crystal structure of calsequestrin from rabbit skeletal muscle sarcoplasmic reticulum. Nat Struct Biol. 1998; 5(6):476-83. DOI: 10.1038/nsb0698-476. View

Yano K, Zarain-Herzberg A . Sarcoplasmic reticulum calsequestrins: structural and functional properties. Mol Cell Biochem. 1994; 135(1):61-70. DOI: 10.1007/BF00925961. View

Tange T, Jensen T, Kjems J . In vitro interaction between human immunodeficiency virus type 1 Rev protein and splicing factor ASF/SF2-associated protein, p32. J Biol Chem. 1996; 271(17):10066-72. DOI: 10.1074/jbc.271.17.10066. View

Nicholls A, Sharp K, Honig B . Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons. Proteins. 1991; 11(4):281-96. DOI: 10.1002/prot.340110407. View

Bruni R, Roizman B . Open reading frame P--a herpes simplex virus gene repressed during productive infection encodes a protein that binds a splicing factor and reduces synthesis of viral proteins made from spliced mRNA. Proc Natl Acad Sci U S A. 1996; 93(19):10423-7. PMC: 38400. DOI: 10.1073/pnas.93.19.10423. View

Krainer A, Mayeda A, Kozak D, Binns G . Functional expression of cloned human splicing factor SF2: homology to RNA-binding proteins, U1 70K, and Drosophila splicing regulators. Cell. 1991; 66(2):383-94. DOI: 10.1016/0092-8674(91)90627-b. View

McCormack J, Denton R . The role of intramitochondrial Ca2+ in the regulation of oxidative phosphorylation in mammalian tissues. Biochem Soc Trans. 1993; 21 ( Pt 3)(3):793-9. DOI: 10.1042/bst0210793. View

Hendrickson W, Horton J, Lemaster D . Selenomethionyl proteins produced for analysis by multiwavelength anomalous diffraction (MAD): a vehicle for direct determination of three-dimensional structure. EMBO J. 1990; 9(5):1665-72. PMC: 551863. DOI: 10.1002/j.1460-2075.1990.tb08287.x. View

10.

Luo Y, Yu H, Peterlin B . Cellular protein modulates effects of human immunodeficiency virus type 1 Rev. J Virol. 1994; 68(6):3850-6. PMC: 236890. DOI: 10.1128/JVI.68.6.3850-3856.1994. View

11.

van den Berg R, Prins F, Lynch N, Schwaeble W, van Es L, Daha M . Intracellular localization of the human receptor for the globular domains of C1q. J Immunol. 1997; 158(8):3909-16. View

12.

Deb T, Datta K . Molecular cloning of human fibroblast hyaluronic acid-binding protein confirms its identity with P-32, a protein co-purified with splicing factor SF2. Hyaluronic acid-binding protein as P-32 protein, co-purified with splicing factor SF2. J Biol Chem. 1996; 271(4):2206-12. DOI: 10.1074/jbc.271.4.2206. View

13.

Green D, Reed J . Mitochondria and apoptosis. Science. 1998; 281(5381):1309-12. DOI: 10.1126/science.281.5381.1309. View

14.

Dedio J, Jahnen-Dechent W, Bachmann M, Muller-Esterl W . The multiligand-binding protein gC1qR, putative C1q receptor, is a mitochondrial protein. J Immunol. 1998; 160(7):3534-42. View

15.

Brunger A, Adams P, Clore G, DeLano W, Gros P, Grosse-Kunstleve R . Crystallography & NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr D Biol Crystallogr. 1998; 54(Pt 5):905-21. DOI: 10.1107/s0907444998003254. View

16.

Jones T, Zou J, Cowan S, Kjeldgaard M . Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr A. 1991; 47 ( Pt 2):110-9. DOI: 10.1107/s0108767390010224. View

17.

Nichols B, Denton R . Towards the molecular basis for the regulation of mitochondrial dehydrogenases by calcium ions. Mol Cell Biochem. 1995; 149-150:203-12. DOI: 10.1007/BF01076578. View

18.

Bernardi P, Broekemeier K, Pfeiffer D . Recent progress on regulation of the mitochondrial permeability transition pore; a cyclosporin-sensitive pore in the inner mitochondrial membrane. J Bioenerg Biomembr. 1994; 26(5):509-17. DOI: 10.1007/BF00762735. View

19.

Lim B, Reid K, Ghebrehiwet B, Peerschke E, Leigh L, Preissner K . The binding protein for globular heads of complement C1q, gC1qR. Functional expression and characterization as a novel vitronectin binding factor. J Biol Chem. 1996; 271(43):26739-44. DOI: 10.1074/jbc.271.43.26739. View

20.

Herwald H, Dedio J, Kellner R, Loos M, Muller-Esterl W . Isolation and characterization of the kininogen-binding protein p33 from endothelial cells. Identity with the gC1q receptor. J Biol Chem. 1996; 271(22):13040-7. DOI: 10.1074/jbc.271.22.13040. View