The McKnight Lab

Director, BUSM Core Facility for Structural NMR

Research

The McKnight lab is interested in the folding, function and dynamics of proteins. A long-time favorite model system is the actin-binding “headpiece” domain of the protein villin. The villin headpiece contains a subdomain of only 35-residues that folds to form a novel three helix structure (HP35). HP35 is one of the shortest amino acid sequences that folds to a monomeric native state in the absence of disulfide bonds or bound metals/ligands. We use NMR, circular dichroism spectroscopy, and other methods, to investigate the stability and motions of proteins using the unique HP35 domain as well as other small protein domains.

Recent Publications

Full list of publications on PubMed

Vugmeyster, L., Rodgers, A, Ostrovsky, D, McKnight, C.J. & Fu, R. Deuteron off-resonance rotating frame relaxation for the characterization of slow motions in rotating and static solid-state proteins, Journal of Magnetic Resonance. 2023. 352, 107493:1-13. PMID: 37271094

Vugmeyster L, Nichols PJ, Ostrovsky D, McKnight CJ, Vögeli B, Slow methyl axes motions in perdeuterated villin headpiece subdomain probed by cross-correlated NMR relaxation measurements. Magnetochemistry. 2023. 9, 33:1-15. PMC9910280

Nichols PJ, Falconer I, Griffin A, Mant C, Hodges R, McKnight CJ, Vögeli B, Vugmeyster L. Deuteration of nonexchangeable protons on proteins affects their thermal stability, side-chain dynamics, and hydrophobicity. Protein Sci. 2020 07; 29(7):1641-1654. PMID: 32356390.

Vugmeyster L, Griffin A, Ostrovsky D, Bhattacharya S, Nichols PJ, McKnight CJ, Vögeli B. Correlated motions of C’-N and Ca-Cß pairs in protonated and per-deuterated GB3. J Biomol NMR. 2018 Oct; 72(1-2):39-54. PMID: 30121872.

Miears HL, Gruber DR, Horvath NM, Antos JM, Young J, Sigurjonsson JP, Klem ML, Rosenkranz EA, Okon M, McKnight CJ, Vugmeyster L, Smirnov SL. Plant Villin Headpiece Domain Demonstrates a Novel Surface Charge Pattern and High Affinity for F-Actin. Biochemistry. 2018 03 20; 57(11):1690-1701. PMID: 29444403.

Xiao R, Dane EL, Zeng J, McKnight CJ, Grinstaff MW. Synthesis of Altrose Poly-amido-saccharides with ß-N-(1>2)-d-amide Linkages: A Right-Handed Helical Conformation Engineered in at the Monomer Level. J Am Chem Soc. 2017 10 11; 139(40):14217-14223. PMID: 28902504.

Falconer IB, Mant CT, McKnight CJ, Vugmeyster L, Hodges R. Optimized purification of a fusion protein by reversed-phase high performance liquid chromatography informed by the linear solvent strength model. J Chromatogr A. 2017 Oct 27; 1521:44-52. PMID: 28942999.

Chin SL, Lu Q, Dane EL, Dominguez L, McKnight CJ, Straub JE, Grinstaff MW. Combined Molecular Dynamics Simulations and Experimental Studies of the Structure and Dynamics of Poly-Amido-Saccharides. J Am Chem Soc. 2016 05 25; 138(20):6532-40. PMID: 27119983.

Harpole KW, O’Brien ES, Clark MA, McKnight CJ, Vugmeyster L, Wand AJ. The unusual internal motion of the villin headpiece subdomain. Protein Sci. 2016 Feb; 25(2):423-32. PMID: 26473993.

Raina D, Agarwal P, Lee J, Bharti A, McKnight CJ, Sharma P, Kharbanda S, Kufe D. Characterization of the MUC1-C Cytoplasmic Domain as a Cancer Target. PLoS One. 2015; 10(8):e0135156. PMID: 26267657.

Chen L, Brown JW, Mok YF, Hatters DM, McKnight CJ. The allosteric mechanism induced by protein kinase A (PKA) phosphorylation of dematin (band 4.9). J Biol Chem. 2015 Jul 17; 290(29):17808. PMID: 26188045.

Brown JW, Bullitt E, Sriswasdi S, Harper S, Speicher DW, McKnight CJ. The Physiological Molecular Shape of Spectrin: A Compact Supercoil Resembling a Chinese Finger Trap. PLoS Comput Biol. 2015 Jun; 11(6):e1004302. PMID: 26067675.

Links

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Facility for Structural NMR

Contact Us

Department of Pharmacology, Physiology & Biophysics
Chobanian & Avedisian School of Medicine
72 East Concord Street, L317
Boston MA 02118-2526

Phone: (617) 358-9553
e-mail: cjmck@bu.edu